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[ABSTRAK
Pendahuluan: Sel punca mesenkimal (SPM) sebagai salah satu alternatif terapi kasus sulit dapat diperoleh dari jaringan adiposa. Kemampuan SPM dalam rekayasa jaringan membutuhkan prosedur implantasi SPM yang aman dan bebas kontaminasi. Tindakan minimal invasive pada kasus cedera medulla spinalis dengan terapi implantasi SPM dapat menyebabkan sel tersebut terpajan radiasi sinar-x c-arm. Viabilitas dan waktu penggandaan populasi (WPP) merupakan salah satu komponen utama keberhasilan prosedur implantasi tersebut. Penelitian ini bertujuan mengetahui efek pajanan sinar-x c-arm terhadap viabilitas dan WPP SPM. Metode: Penelitian ini adalah penelitian eksperimental SPM jaringan adiposa pasca cryopreservation. Sel punca pasca thaw dan propagasi kemudian dilakukan pajanan radiasi sinar-x dengan c-arm. Sel punca kemudian di kultur untuk menilai viabilitas dan waktu penggandaan populasi. Uji Generalized Linear Model untuk menilai perbedaan viabilitas antara besar dosis radiasi. Uji Spearman menilai korelasi perbedaan viabilitas kelompok pasca-radiasi, dan pasca radiasi dan kultur. Uji Kruskall-Wallis menilai WPP kelompok pasca-radiasi antara masing-masing besar dosis. Uji Wilcoxon menilai WPP antara kelompok pre-radiasi dengan kelompok pasca-radiasi. Hasil: Waktu konfluensi kultur sel pasca radiasi rata-rata 4.33 hari. Rerata perbedaan viabilitas antara besar dosis radiasi tidak terdapat perbedaan yang bermakna secara statistik (p>0.05). Didapatkan korelasi positif viabilitas pasca radiasi dengan besar dosis radiasi namun tidak bermakna secara statistik (p>0.05) namun didapatkan korelasi negatif viabilitas pasca radiasi dan kultur dengan besar dosis radiasi dan bermakna secara statistik. Tidak didapatkan perbedaan bermakna median WPP antara kelompok pre-radiasi dan pasca-radiasi (p>0.05) dan perbedaan WPP diantara kelompok pasca radiasi (p>0.05). Kesimpulan: Tidak terdapat perbedaan secara statistic viabilitas dan WPP SPM jaringan adiposa pasca pajanan radiasi sinar-x c-arm sampai sampai dosis radiasi 32.34 mSv.

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ABSTRACT
Introduction. The use of adipose tissue derived mesenchymal stem cells (MSCs)in tissue engineering require implantation procedure that is safe and free of contamination. Minimally invasive procedure in the case of spinal cord injury using a c-arm device for MSC implantation causes x-ray exposure to the implanted cells. Viability and population doubling time (PDT) is a major component of the success of the implantation procedure. This study aims to determine the effect of c-arm x-ray exposure on MSC viability and PDT. Methods. This was an experimental study that used cryopreserved adipose tissue derived MSCs. Cells were thawed, propagated, and exposed to varying doses of c-arm x-ray radiation. Stem cell viability was measured, and then the cells were cultured to assess their PDT. Generalized linear models test was used to compare cell viability between post-thaw, post-propagation, post-radiation, post-culture post-radiation, and control and between radiation dose groups. Kruskal-Wallis test assessed PDT between various radiation doses in post-radiation groups. Wilcoxon test assessed PDT between pre-radiation and post-radiation groups. Results. Mean confluence period of adipose MSCs post radiation was 4.33 days. There was no statistically significant difference in MSC mean viability after exposure to x-ray radiation between each group and control (p>0.05). There was no significant positive correlation between post radiation viability and radiation dose (p > 0.05), however, there was significant negative correlation between post radiation post culture viability and radiation dose. There were no significant differences in PDT between pre- and post-culture post radiation groups and between various radiation doses in post-radiation groups (p>0.05). Conclusion. No statistical differences in MSC viability and PDT after x-ray radiation exposure of c-arm up to 32.34 mSv;Introduction. The use of adipose tissue derived mesenchymal stem cells (MSCs)in tissue engineering require implantation procedure that is safe and free of contamination. Minimally invasive procedure in the case of spinal cord injury using a c-arm device for MSC implantation causes x-ray exposure to the implanted cells. Viability and population doubling time (PDT) is a major component of the success of the implantation procedure. This study aims to determine the effect of c-arm x-ray exposure on MSC viability and PDT. Methods. This was an experimental study that used cryopreserved adipose tissue derived MSCs. Cells were thawed, propagated, and exposed to varying doses of c-arm x-ray radiation. Stem cell viability was measured, and then the cells were cultured to assess their PDT. Generalized linear models test was used to compare cell viability between post-thaw, post-propagation, post-radiation, post-culture post-radiation, and control and between radiation dose groups. Kruskal-Wallis test assessed PDT between various radiation doses in post-radiation groups. Wilcoxon test assessed PDT between pre-radiation and post-radiation groups. Results. Mean confluence period of adipose MSCs post radiation was 4.33 days. There was no statistically significant difference in MSC mean viability after exposure to x-ray radiation between each group and control (p>0.05). There was no significant positive correlation between post radiation viability and radiation dose (p > 0.05), however, there was significant negative correlation between post radiation post culture viability and radiation dose. There were no significant differences in PDT between pre- and post-culture post radiation groups and between various radiation doses in post-radiation groups (p>0.05). Conclusion. No statistical differences in MSC viability and PDT after x-ray radiation exposure of c-arm up to 32.34 mSv, Introduction. The use of adipose tissue derived mesenchymal stem cells (MSCs)in tissue engineering require implantation procedure that is safe and free of contamination. Minimally invasive procedure in the case of spinal cord injury using a c-arm device for MSC implantation causes x-ray exposure to the implanted cells. Viability and population doubling time (PDT) is a major component of the success of the implantation procedure. This study aims to determine the effect of c-arm x-ray exposure on MSC viability and PDT. Methods. This was an experimental study that used cryopreserved adipose tissue derived MSCs. Cells were thawed, propagated, and exposed to varying doses of c-arm x-ray radiation. Stem cell viability was measured, and then the cells were cultured to assess their PDT. Generalized linear models test was used to compare cell viability between post-thaw, post-propagation, post-radiation, post-culture post-radiation, and control and between radiation dose groups. Kruskal-Wallis test assessed PDT between various radiation doses in post-radiation groups. Wilcoxon test assessed PDT between pre-radiation and post-radiation groups. Results. Mean confluence period of adipose MSCs post radiation was 4.33 days. There was no statistically significant difference in MSC mean viability after exposure to x-ray radiation between each group and control (p>0.05). There was no significant positive correlation between post radiation viability and radiation dose (p > 0.05), however, there was significant negative correlation between post radiation post culture viability and radiation dose. There were no significant differences in PDT between pre- and post-culture post radiation groups and between various radiation doses in post-radiation groups (p>0.05). Conclusion. No statistical differences in MSC viability and PDT after x-ray radiation exposure of c-arm up to 32.34 mSv]

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Jabatan yang diemban notaris merupakan jabatan kepercayaan, untuk itulah seorang notaris harus bertanggung jawab bukan hanya kepada diri notaris tapi juga kepada masyarakat. Bertanggung jawab kepada diri sendiri dapat ditunjukkan dengan notaris bekerja untuk melaksanakan kepercayaan yang diberikan kepadanya dengan tidak berpihak sebagaimana diatur dalam Pasal 16 ayat (1) huruf A UUJN. Salah satu contoh dari akta notaris adalah akta pengakuan utang yang merupakan akta partij, jenis akta ini merupakan penyesuaian kehendak antara kedua belah pihak, tentu sepanjang memenuhi syarat sah perjanjian dalam Pasal 1320 KUH Perdata. Kasus dalam Putusan MPWN Provinsi DKI Jakarta Nomor:12/Pts/Mj.PWN.Prov.DKIJakarta/IX/2021 menunjukkan adanya keberpihakan notaris dalam pembuatan akta pengakuan utang. Adapun rumusan masalah dalam tesis adalah akibat hukum dari akta pengakuan utang yang dibuat di luar kehendak.dan tanggung jawab notaris yang berpihak. Metode penelitian yang digunakan adalah yuridis-normatif dengan tipe penelitian kualitatif. Hasil dari penelitian adalah dikarenakan akta pengakuan utang dibuat di luar kehendak salah satu pihak maka melanggar syarat subjektif yaitu kesepakatan dan menyebabkan akta dapat dibatalkan. Selanjutnya akta pengakuan utang berisikan perjanjian utang-piutang berserta jaminan sehingga melanggar syarat objektif maka batal demi hukum. Berdasarkan Pasal 16 ayat (1) huruf A UUJN, notaris berkewajiban untuk tidak berpihak, apabila hal tersebut dilanggar maka berdasarkan Pasal 9 ayat (1) UUJN, notaris dapat diberhentikan sementara dari jabatannya. Pengaduan kepada Majelis Pengawas Notaris dan pemberian sanksi kepada notaris tetap tidak membatalkan akta, sehingga apabila ada pihak yang merasa dirugikan dengan terbitnya suatu akta autentik maka dapat melakukan gugatan perdata kepada pengadilan negeri setempat. ......Position of a notary is a position of trust, a notary must be responsible not only to themselves but also to the community. Being responsible can be shown carrying out the trust given to the with impartially as regulated in Article 16 paragraph (1) letter A of UUJN. Example of a notarial deed is a debt acknowledgment deed which is a partij deed, this type of deed is an adjustment will between the two parties, as long as it fulfills the Article 1320 of the Civil Code. The case in the Decision of the MPWN of DKI Jakarta Province Number: 12/Pts/Mj.PWN.Prov.DKIJakarta/IX/2021 shows the notary's partiality in making debt acknowledgment deed. The research questions are the legal consequences of the debt acknowledgment deed made against the will and responsibility of notary’s impartiality. The research method is juridical-normative with qualitative research. The result is the debt acknowledgment deed has violated the subjective conditions and causes the deed to be voidable. The debt acknowledgment deed contains a debt agreement along with collateral so that it violates the objective conditions which can be null and void. Based on Article 16 paragraph (1) letter A UUJN, notary is obliged to not take sides, if it is violated then based on Article 9 paragraph (1) UUJN, the notary can be temporarily suspended. Complaints to the Notary Supervisory Council and imposing sanctions on the notary still do not cancel the deed, so if there are parties who feel aggrieved by the deed, they can file a civil lawsuit with the local district court.

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Hati merupakan organ yang memiliki kemampuan regenerasi tinggi setelah mengalami kerusakan. Sel punca mesenkimal asal tali pusat merupakan sumber progenitor hati yang dapat ditranplantasikan dan dapat digunakan pada kasus kerusakan hati yang parah. Kerusakan hati yang parah akan memunculkan sel oval sebagai pertahanan tingkat ke dua. Proses regenerasi hati yang diperantarai sel oval sangat kompleks karena melibatkan sitokin, faktor pertumbuhan, hormon dan morfogen. DLK1 (Delta-Like 1 homolog) merupakan salah satu morfogen yang diekspresikan kembali pada kasus kerusakan hati dengan kondisi proliferasi hepatosit yang dihambat. DLK1 diekspresikan oleh sel oval dalam jumlah yang terbatas. Penelitian ini bertujuan mengetahui ekspresi DLK1 dan proliferasi hepatosit yang dinilai menggunakan Ki67 pada kerusakan yang diinduksi 2AAF/CCl₄. Selain itu juga akan dinilai pengaruh sel punca pada ekspresi DLK1 dan proliferasi hepatosit yang dinilai menggunakan Ki67 pada saat proses regenerasi hati. Penelitian ini menggunakan 30 tikus jantan strain Wistar berusia 8 minggu yang dibagi menjadi 5 kelompok (n=6). Proses Induksi kerusakan hati menggunakan 2AAF/CCl₄ selama 12 minggu kemudian diberikan injeksi sel punca mesenkimal asal tali pusat manusia dengan dosis 1x10⁶ sel melalui vena ekor. Dua kelompok (kontrol dan induksi 2AAF/CCl₄) diterminasi pada akhir minggu ke-12 sebagai model kerusakan hati sedangkan tiga kelompok lainnya (kontrol, kelompok dengan sel punca dan kelompok tanpa sel punca diterminasi pada akhir minggu ke-14. Pada penelitian ini ditemukan bahwa terdapat perbedaan signifikan ekspresi DLK1 namun tidak terdapat perbedaan signifikan pada tingkat proliferasi hepatosit yang dinilai dengan Ki67 pada kerusakan hati yang diinduksi 2AAF/CCl₄. Sedangkan pada regenerasi hati tidak ditemukan perbedaan signifikan ekspresi DLK1 dan Ki67 antara kelompok yang diberikan sel punca dan tidak diberikan sel punca. ......The liver is an organ that has a high regeneration ability after being injured. Mesenchymal stem cells from the human umbilical cord are transplanted sources of liver progenitors and can be used in cases of severe liver injury. Severe liver damage will bring out oval cells as a second level defense. The process of liver regeneration which is mediated by oval cells is very complex because it involves cytokines, growth factors, hormones and morphogens. DLK1 (Delta-Like 1 homologue) is one of the morphogens that is expressed again in cases of liver injury with inhibited hepatocyte proliferation. DLK1 is expressed in subpopulation in oval cells compartement of rat liver. This study aims to determine the expression of DLK1 and hepatocyte proliferation which was assessed using Ki67 in the 2AAF/CCl₄ induced severe injury. It will also be assessed the effect of mesenchymal stem cells on DLK1 expression and hepatocyte proliferation which was assessed using Ki67 during the liver regeneration process. This study used 30 male 8-week-old Wistar strain rats divided into 5 groups (n = 6). The process of induction of liver injury using 2AAF/CCl₄ for 12 weeks was then given mesenchymal stem cell injection from human umbilical cord at a dose of 1x10⁶ cells through the tail vein. Two groups (control and 2AAF/CCl₄ groups) were terminated at the end of the 12th week as models of liver injury while the other three groups (control, groups with stem cells and groups without stem cells were terminated at the end of week 14. In this study it was found that there was a significant difference in DLK1 expression but there was no significant difference in the rate of hepatocyte proliferation assessed by Ki67 in 2AAF/CCl₄ induced liver injury, whereas in liver regeneration there was no significant difference in DLK1 and Ki67 expression between groups given stem cells and not given stem cells.

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Pendahuluan: Osteoartritis (OA) adalah penyakit sendi degeneratif yang ditandai oleh kerusakan tulang rawan. Kemampuan regenerasi tulang rawan artikular yang terbatas menimbulkan tantangan dalam pengobatan. Eksosom sel punca mesenkimal (SPM) telah menunjukkan potensi regenerasi struktur tulang rawan pada studi-studi in vivo pada hewan kecil sebelumnya. Penelitian ini bertujuan untuk membandingkan efektivitas injeksi intra-artikular eksosom SPM dari jaringan adiposa dan hyaluronic acid (HA) terhadap regenerasi tulang rawan model osteoartritis domba Metode: Studi in vivo melibatkan 18 domba jantan yang diinduksi OA melalui menisektomi. Domba kemudian dirandomisasi dan dibagi menjadi tiga kelompok perlakuan: Kelompok 1 (eksosom SPM adiposa + HA); Kelompok 2 (eksosom SPM adiposa); Kelompok 3 (HA). Pemeriksaan struktur dan mikrostruktur dilakukan 6 minggu pasca perlakuan. Penilaian mikroskopik menggunakan gambaran histologi dengan skor pineda, regenerasi tulang rawan dinilai dari pemeriksaan histokimia and immunohistokimia, dan pemeriksaan mikrotopografi dinilai dengan scanning electron microscope (SEM) Hasil dan Diskusi: Regenerasi tulang rawan pada kelompok kombinasi eksosom SPM adiposa + HA memiliki area kartilago hialin yang lebih luas dibandingkan dengan eksosom SPM adiposa atau HA saja (40,38 ± 9,35 % vs 34,93 ± 2,32 vs 31,08 ± 3,47; p = 0,034) dan area fibrokartilago yang lebih sempit dibandingkan dengan eksosom SPM adiposa atau HA saja (13,06 ± 2,21 vs 18,67 ± 3,13 vs 28,14 ± 3,67; p = 0,037). Gambaran mikrotopografi didapatkan permukaan jaringan jauh lebih homogen dan memiliki permukaan yang lebih halus pada kelompok kombinasi eksosom SPM adiposa + HA dibandingkan kelompok eksosom SPM adiposa HA saja Kesimpulan: Pada OA sendi lutut model domba yang mendapatkan injeksi kombinasi eksosom SPM jaringan adiposa + HA memiliki regenerasi tulang rawan yang lebih baik dibandingkan dengan injeksi eksosom SPM jaringan adiposa atau HA saja ......Introduction: Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage damage. The limited regenerative capability of articular cartilage poses a therapeutic challenge. Mesenchymal stem cell (MSC) exosomes have shown potential in regenerating cartilage structure in previous in vivo studies on small animals. This study aims to compare the effectiveness of intra-articular injections of adipose-derived MSC exosomes and hyaluronic acid (HA) on cartilage regeneration in a sheep osteoarthritis model. Methods: This in vivo study involved 18 male sheep induced with OA through meniscectomy. The sheep were randomized and divided into three intervention groups: Group 1 (adipose MSC exosomes + HA), Group 2 (adipose MSC exosomes), and Group 3 (HA). Structural and microstructural assessments were conducted 6 weeks post-intervention. Microscopic evaluation using histological scoring with the Pineda score, cartilage regeneration assessment through histochemical and immunohistochemical examinations, and microtopographic examination using a scanning electron microscope (SEM) were performed. Results and Discussion: Cartilage regeneration in the combination group of adipose MSC exosomes + HA exhibited a larger area of hyaline cartilage compared to adipose MSC exosomes or HA alone (40.38 ± 9.35% vs. 34.93 ± 2.32% vs. 31.08 ± 3.47%; p = 0.034) and a smaller area of fibrocartilage compared to adipose MSC exosomes or HA alone (13.06 ± 2.21% vs. 18.67 ± 3.13% vs. 28.14 ± 3.67%; p = 0.037). Microtopographic examination showed a much more homogeneous and smoother cartilage surface in the combination group of adipose MSC exosomes + HA compared to the adipose MSC exosomes or HA groups alone. Conclusion: In a sheep knee OA model, intra-articular injection of a combination of adipose-derived MSC exosomes + HA can enhance cartilage regeneration compared to injections of adipose-derived MSC exosomes or HA alone.

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Diabetes melitus (DM) menyebabkan gangguan saraf autonom, sensorik, dan motorik, terutama di kaki dan pergelangan kaki yang menyebabkan perubahan postur kaki dan deformitas. Artritis pergelangan kaki penyandang DM mengakibatkan gangguan fungsional sehingga artrodesis merupakan suatu opsi tata laksana pembedahan. Sayangnya, gangguan metabolik DM mengakibatkan komplikasi yang tak jarang yakni non-union. Terapi sel dan derivatnya merupakan opsi terapi regeneratif untuk meningkatkan kesembuhan tulang. Pembuatan model artritis hewan DM dengan injeksi streptozotosin (STZ), diet tinggi lemak (HFD), dan injeksi complete freud adjuvant (CFA) dilanjutkan studi eksperimental in vivo dengan fokus hasil augmentasi fusi dengan granul hidroksiapatit (HA), sel punca mesenkimal asal tali pusat (SPM-TP), dan sekretom jaringan adiposa (JA). Sebanyak 16 sampel kaki dibagi menjadi 3 kelompok: kontrol negatif (kelompok 1), kontrol positif yang diberikan autologous bone graft (kelompok 2), dan perlakuan yang diberikan HA, SPM-TP, dan sekretom-JA (kelompok 3). Dilakukan evaluasi parameter klinis, radiologis, profil histomorfometris, dan ekspresi biomarker di subjek model artritis DM tikus Sprague Dawley (SD). Status DM tercapai setelah induksi STZ dengan rerata kadar glukosa 421 ± 27,16 mg/dL. Kelompok artritis menunjukkan perubahan diameter ankle yang bermakna dibanding kontrol serta perubahan radiologis sendi pergelangan kaki. Artritis berat (skor 3) ditemukan di mayoritas (80%) sampel kelompok 1 yang merupakan kontrol negatif (hanya induksi DM). Kelompok perlakuan menunjukkan skor artritis terendah serta osifikasi di sisi anterior tibiotalar. Terdapat perbedaan bermakna osteokalsin (p = 0,017) dan gen chordin (p = 0,003) antara ketiga kelompok. Simpulan: Model artritis DM pada tikus SD berhasil dibuat dengan injeksi STZ dan HFD serta induksi artritis kronik dengan injeksi CFA di sendi pergelangan kaki selama 4 minggu. Pemberian SPM-TP, sekretom JA, dan granul HA menunjukkan skor artritis yang lebih rendah. Namun, pemberian ketiga bahan tersebut tidak menghasilkan gambaran fusi yang lebih baik, serta tidak meningkatkan kadar osteokalsin, namun menghasilkan jumlah chordin (protein inhibisi BMP) yang lebih kecil dibandingkan baku standar. ......Diabetes mellitus (DM) can cause disturbances in the autonomic, sensory, and motor nerves, particularly in the feet and ankles, eventually leading to changes in foot posture and specific deformities. The advancement of management using stem cells and their secretome has shown promising outcomes. A model of DM arthritis can be created by inducing experimental animals with streptozotocin (STZ). In the DM arthritis model, the evaluation of ankle arthrodesis augmented with umbilical cord mesenchymal stem cell (MSC-Uc) and adipose tissue secretome (Secretome-AD) can be carried out to observe the existing outcomes. This study is divided into two stages wherein the first stage involves creating an arthritis model in DM animals. The study utilizes a pretest-posttest design to measure clinical and laboratory parameters before and after treatment. Subsequently, the second stage involves an in vivo experimental study focusing on the outcomes of fusion augmentation with MSC-Uc, secretom-AD, and HA granule. The second stage of the study includes assessments using single-blinding methods for clinical, radiological, histomorphometric profile, and biomarker expression in the SD rat model of DM arthritis. DM status was achieved after STZ injection, with an average glucose level of 421 ± 27.16 mg/dL. The final diameter averages in groups 1 – 3, which were not induced with arthritis (9.64 ± 0.49 mm), significantly differed from group 4 (12.50 ± 0.87 mm, p = 0.003) and 5 (11.85 ± 0.74 mm, p = 0.037). The arthritis groups showed radiological changes in the ankle joint. After modeling, there was a significant increase in fasting blood glucose compared to pre-modeling measurements. Severe arthritis (score 3) was found in the majority (80%) of samples in group 1, which served as the negative control (DM induction only). Anova test results for the IHC parameter showed significant differences (p = 0.017) in osteocalcin and chordin gene (p = 0.003) among the three groups. Conclusion: A model of DM arthritis in SD rats was successfully created by STZ and HFD induction, followed by the induction of chronic arthritis with CFA injection in the ankle joint for 4 weeks. The administration of MSC-Uc, secretome-AD, and HA granule indicated lower arthritis scores. However, the administration of these three substances did not produce a better fusion picture, nor did it increase osteocalcin levels, but it resulted in a smaller amount of chordin (BMP inhibition protein) compared to the standard.

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ABSTRAK
Pendahuluan. Sel punca mesenkimal merupakan jawaban untuk berbagai penyakit, termasuk orthopedi. Meskipun jumlah terbatas, prosedur invasif, nyeri, dan sel yang relatif sedikit, sumsum tulang masih menjadi sumber utama. Adiposa menjadi alternatif menjanjikan dengan kemampuan sebanding. Dengan meningkatnya harapan hidup, jumlah pasien tua meningkat dan menjadi sangat potensial untuk aplikasi sel punca. Namun, timbul kontroversi mengenai kualitas sel punca pada penuaan. Metode Penelitian. Penelitian dilakukan di Unit Pelayanan Terpadu Teknologi Kedokteran Sel Punca Rumah Sakit Cipto Mangunkusumo-Fakultas Kedokteran Universitas Indonesia, Jakarta sejak Oktober 2015 - Maret 2016. 12 subjek dibagi menjadi tiga kelompok usia; 15-30 tahun, 31-40 tahun, dan 41-55 tahun dan dilakukan pengambilan sumsum tulang krista iliaka posterior dan adiposa, kemudian dilakukan isolasi dan kultur sel punca mesenkimal. Peneliti melakukan analisis karakteristik biologis, waktu penggandaan populasi, diferensiasi osteogenik, dan pewarnaan Alizarin. Seluruh data dianalisis dengan SPSS 20. Temuan Penelitian. Karakteristik biologis dan pewarnaan Alizarin Red menunjukkan tidak ada perbedaan bermakna sel punca mesenkimal sumsum tulang dan adiposa pada kelompok usia sama(p>0,05). Waktu penggandaan populasi menunjukkan adanya perbedaan signifikan sel punca mesenkimal sumsum tulang dan adiposa pada kelompok 31-40 tahun(p=0,028) dan 41-55 tahun(p=0,035) Kesimpulan. Sel punca mesenkimal adiposa menunjukkan karakteristik biologis, waktu penggandaan populasi, dan diferensiasi osteogenik yang konstan. Sel punca mesenkimal sumsum tulang menunjukkan waktu penggandaan populasi yang menurun seiring usia, berbeda dengan karakteristik biologis dan diferensiasi osteogenik. Adiposa dapat menjadi pilihan sumber sel punca mesenkimal pada setiap golongan usia.

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ABSTRACT
Introduction. Mesenchymal stem cell is the answer of many medicine problems, including orthopaedic. Bone marrow is still the main source. Because of limited source, invasive procedure, pain, and relative less cell, adipose will be promising source with equal regenerating and differentiating ability. Along with increasing life expectancy, geriatric population is increasing as well as the potential need for stem cell application. Yet there is still controversy about stem cell quality in aging. Methods. This study was conducted in Stem Cell Medical Technology Integrated Service Unit Cipto Mangunkusumo General Hospital-Faculty of Medicine Universitas Indonesia, Jakarta, October 2015 - March 2016. 12 patients were divided into 3 age group; 15-30 year, 31-40 year, and 41-55 year. Bone marrow from posterior iliac crest and adipose tissue were collected, mesenchymal stem cell isolation and culture were done subsequently. Biological characterization, Population Doubling Time, osteogenic differentiation, and alizarin red assay were carried out. All data was analyzed using SPSS 20. Results. No significant difference was observed in biological characteristic and Alizrin red assay of bone marrow and adipose mesenchymal stem cell among age group (p>0.05). There is significant difference in Population Doubling time in 31- 40 year group(p=0.000) and 41-55 year group(p=0.000). Conclusions. Adipose mesenchymal stem cell had steady biological characteristic, Population Doubling Time, and osteosteogenic differentiation. Bone marrow mesenchymal stem cell had increasing population doubling time in increasing age, apart from biological characteristic and osteogenic differentiation. Adipose could be the source of choice in harvesting mesenchymal stem cell at any age.

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Latar Belakang. Sumsung tulang merupakan sumber sel punca mesenkimal SPM yang paling banyak digunakan selain jaringan lemak sebagai sumber pengganti yang menjanjikan. Peningkatan penggunaan SPM membutuhkan kemampuan untuk melakukan subkultur pasase SPM. Untuk mengumpulkan dan menyimpan SPM dalam waktu tertentu tanpa mengubah karakter SPM maka dilakukan kriopreservasi. Penelitian ini bertujuan meningkatkan pemahaman efek pasase terhadap penuaan sel punca mesenkimal sumsum tulang dan jaringan lemak yang dikriopreservasi.Metode. Penelitian ini merupakan studi analitik observasional yang dilaksanakan di UPT-TK Sel Punca RSCM FKUI April 2016 - September 2016. Sampel penelitian adalah sel punca mesenkimal sumsum tulang dan jaringan lemak pasase pertama yang dikriopreservasi 1 dan 2 kali. Dilakukan pengukuran terhadap ukuran sel, viabilitas sel, population doubling time PDT, colony forming unit dan penghitungan persentase sel yang menua. Data pasase dianalisis dengan multiple comparison ANOVA dengan Tukey HSD correction dan student t-test menggunakan program SPSS 23. Hasil. Terdapat perbedaan yang signifikan antara kedua kelompok kriopreservasi SPM sumsum tulang dalam PDT, viabilitas, dan ukuran sel pada P6 dengan p ...... Introduction. Bone marrow is still the gold standard source of MSC, but adipose tissue became a promising alternative source. Passage and cryopreservation are effective ways to multiply, pool and store MSC without altering its function. The aim of this research was to enhance the knowledge of the effect of passage on senescence profile of cryopreserved human bone marrow and adipose derived MSC.Method. This research was an observational analytic study to analyze population doubling time PDT, cell size, viability, colony forming unit and percentage of senescent cells and done in UPT ndash TK Sel Punca RSCM FKUI, during April to September 2016. The samples were bone marrow and adipose MSC at passage one, which were cryopreserved for the first and second time. Cryopreservastion groups were analyzed using student t test while inter passage was analyzed using ANOVA test. Result. There were significant differences between both cryopreserved bone marrow groups in PDT, viability and cell size in P6, p

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[ABSTRAK
Pendahuluan. Sel punca mesenkimal (SPM) sangat menjanjikan dalam bidang rekayasa jaringan karena sifatnya yang multipoten, cepat berproliferasi, dan berkemampuan tinggi untuk beregenerasi. SPM sumsum tulang dapat menjadi terapi pilihan nekrosis avaskular (AVN) kaput femur yang banyak diderita oleh pasien lupus eritematosus sistemik (LES) pada masa sekarang ini. SPM sumsum tulang penderita LES mengalami gangguan fenotip, proliferasi, diferensiasi. Terapi SPM pada AVN kaput femur dapat menggunakan donor otologus yang dilaporkan memberikan hasil luaran yang baik dan keamanan yang signifikan. Oleh karena itu, diperlukan penelitian untuk mengetahui potensi, karakteristik, dan diferensiasi SPM sumsum tulang pasien LES yang dihubungkan dengan usia. Metode. Penelitian ini adalah penelitian in vitro yang meneliti 4 subjek penderita LES di Rumah Sakit Cipto Mangunkusumo Jakarta. Aspirat SPM sumsum tulang dilakukan isolasi, ekspansi dan diferensiasi. Analisis statistik menggunakan uji korelasi spearman untuk melihat hubungan usia pasien LES dengan waktu konfluensi, jumlah sel konfluens dan waktu diferensiasi osteogenik, kondrogenik, dan adipogenik. Hasil dan Diskusi. Rerata jumlah sel konfluens adalah 7.44 x 105 ± 3.06 x 105 sel/ml, rerata waktu konfluens adalah 20.75 ± 4.99 hari, median waktu diferensiasi adipogenik yaitu 17.5 hari (rentang 14-21), waktu diferensiasi osteogenik dan kondrogenik yaitu 21 hari. Terdapat korelasi positif bermakna antara usia penderita LES dengan waktu konfluens SPM (p<0.001) dan korelasi negatif bermakna antara usia penderita LES dengan jumlah sel konfluens SPM (p<0.001). Simpulan. SPM sumsum tulang krista iliaka penderita LES mampu diisolasi, berproliferasi dan berdiferensiasi. SPM sumsum tulang penderita LES memiliki waktu konfluens dan waktu diferensiasi yang lebih lama dan jumlah sel konfluens yang lebih sedikit.

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ABSTRACT
Introduction. Mesenchymal stem cells (MSC) is very promising in the field of tissue engineering because it is multipotent, rapidly proliferate, and high ability to regenerate bone marrow. BM-MSC may be treatment of choice of avascular necrosis (AVN) of femoral head that affects many systemic lupus erythematosus (SLE) patients at the present time. BM-MSC of SLE patients has impairment in phenotype, proliferation, and differentiation. Mesenchymal stem cell therapy on femoral head AVN which use autologous donors are reported deliver good outcomes and safety. Therefore, research is needed to determine the potency, characteristics, and differentiation of BM-MSC in patients with SLE and related with age. Methods. This study is in vitro study that examined four subjects as SLE patients in Cipto Mangunkusumo Hospital. BM-MSC of SLE patients is performed isolation, expansion and differentiation. Statistical analysis using pearson and spearman correlation test to see the correlation of age of SLE patients with confluence time, the number of confluence cells and differentiation time. Result and Discussion. Mean of confluent cell numbers is 7.44 x 105 ± 3.06 x 105cells/ml, mean of confluent time is 20.75 ± 4.99 days, median of adipogenic differentiation time is 17.5 days (range 14-21), osteogenic and chondrogenic differentiation time is 21 days. There is a positive correlation between patient?s age with confluence time (p <0.001) and negative correlation with MSC confluence cell count (p <0.001). Conclusion. BM-MSC form iliac crest in patients with SLE can be isolated, proliferated and differentiated. BM-MSC of SLE patients has longer confluence time and differentiation time and lower confluence cell count., Introduction. Mesenchymal stem cells (MSC) is very promising in the field of tissue engineering because it is multipotent, rapidly proliferate, and high ability to regenerate bone marrow. BM-MSC may be treatment of choice of avascular necrosis (AVN) of femoral head that affects many systemic lupus erythematosus (SLE) patients at the present time. BM-MSC of SLE patients has impairment in phenotype, proliferation, and differentiation. Mesenchymal stem cell therapy on femoral head AVN which use autologous donors are reported deliver good outcomes and safety. Therefore, research is needed to determine the potency, characteristics, and differentiation of BM-MSC in patients with SLE and related with age. Methods. This study is in vitro study that examined four subjects as SLE patients in Cipto Mangunkusumo Hospital. BM-MSC of SLE patients is performed isolation, expansion and differentiation. Statistical analysis using pearson and spearman correlation test to see the correlation of age of SLE patients with confluence time, the number of confluence cells and differentiation time. Result and Discussion. Mean of confluent cell numbers is 7.44 x 105 ± 3.06 x 105cells/ml, mean of confluent time is 20.75 ± 4.99 days, median of adipogenic differentiation time is 17.5 days (range 14-21), osteogenic and chondrogenic differentiation time is 21 days. There is a positive correlation between patient’s age with confluence time (p <0.001) and negative correlation with MSC confluence cell count (p <0.001). Conclusion. BM-MSC form iliac crest in patients with SLE can be isolated, proliferated and differentiated. BM-MSC of SLE patients has longer confluence time and differentiation time and lower confluence cell count.]

Abstrak :
Latar Belakang: Obesitas telah menjadi masalah kesehatan besar di dunia. PEMF merupakan modalitas penyembuhan obesitas karena mampu menghambat adipogenesis. Hingga kini, belum dapat dipahami proses molekuler yang mendasari mekanisme penghambatan adipogenesis oleh PEMF. Adipogenesis diketahui melibatkan faktor transkripsi PPARγ yang berperan dalam pengaktifan gen-gen adipogenik, di antaranya ADIPOQ. PPARγ terkekspresi tinggi pada tahap awal adipogenesis dan ADIPOQ terekspresi tinggi pada tahap terminasi adipogenesis. Kedua gen tersebut dapat dijadikan penanda terjadinya adipogenesis. Penelitian ini bertujuan untuk mengetahui tingkat ekspresi PPARγ dan ADIPOQ pada MSC yang dipajan PEMF dan MSC yang tidak dipajan PEMF. Metode: Sampel RNA diisolasi dari masing-masing kelompok perlakuan pada hari ke-0 (kalibrator), 2, 4, 7, dan 14. Ekspresi gen PPARγ dan ADIPOQ dianalisis menggunakan metode qRT-PCR. Pajanan PEMF diberikan dengan intensitas Bmax=2 mT, f= 75 Hz, dalam waktu 10 menit sehari selama 14 hari masa adipogenesis. Sebagai data pelengkap dilakukan pengamatan terhadap morfologi dan jumlah sel berdasarkan hasil gambaran menggunakan mikroskop. Hasil: Hasil analisis qRT-PCR menunjukkan ekspresi PPARγ dan ADIPOQ pada kelompok PEMF lebih rendah dibanding dengan kelompok kontrol. Pada hari ke-2 dan hari ke-14, terdapat perbedaan bermakna ekspresi PPARγ dan ADIPOQ antara kelompok PEMF dan kelompok kontrol (p<0,05). Pada hari ke-7, ekspresi PPARγ dan ADIPOQ mulai ditekan kembali pada kelompok PEMF, ditandai dengan tidak adanya perbedaan bermakna antara kenaikan ekspresi PPARγ dan ADIPOQ di hari ke-4 menuju hari ke-7 (p>0,05). Penghambatan ekspresi gen sejalan dengan hasil pengamatan morfologi dan jumlah sel. Kesimpulan: PEMF memiliki efek penghambatan terhadap adipogenesis sel punca mesenkimal. Hasil penelitian menunjukkan bahwa pajanan PEMF dapat menekan ekspresi PPARγ dan ADIPOQ, perkembangan morfologi, dan jumlah sel selama masa adipogenesis. ......Background: Obesity has become a major health problem in the world. PEMF is known as a modality for obesity treatment because its ability to inhibit adipogenesis. But until now, the molecular processes of adipogenesis inhibition by PEMF is remain unknown. Adipogenesis process involve the transcription factor, PPARγ, which plays a role in activating adipogenic genes, including ADIPOQ. PPARγ is highly expressed at the early stages of adipogenesis and ADIPOQ is highly expressed at the termination of adipogenesis. Both of these genes can be used as markers of adipogenesis. This study aimed to determine the level of PPARγ and ADIPOQ expression on MSC exposed by PEMF and MSC that are not exposed by PEMF. Method: Total RNA was extrected from samples of each treatment group on day 0 (calibrator), 2, 4, 7, and 14. The expression level of PPARγ and ADIPOQ were analyzed using the qRT-PCR method. Exposure to PEMF with Bmax = 2 mT, f = 75 Hz, for 10 minutes a day in 14 days of adipogenesis. Observations on the morphology and the number of cells were analyzed using a microscope imaging. Result: The results of the qRT-PCR analysis showed expression of PPARγ and ADIPOQ in the PEMF group is lower than the control group. On the day 2 anda day 14, there were significant differences in the expression of PPARγ and ADIPOQ between the PEMF group and the control group (p <0.05). On day 7, expression of PPARγ and ADIPOQ suppressed in the PEMF group, marked by a and no significant difference between increases PPARγ and ADIPOQ on day 4 to day 7 (p> 0.05). Inhibition of gene expression is in line with the results of morphology and number of cells. Conclusion: Adipogenesis inhibition in the PEMF group was better than the control group. The results showed that the effect of PEMF and length of exposure can suppress PPARγ and ADIPOQ expression, cell morphology, and the number of cells during the period of adipogenesis.

Abstrak :
Pendahuluan: Efek hiperglikemik dan produk Advanced Glycation Endproduct (AGE) dari diabetes mellitus (DM) sering dikaitkan dengan komplikasi muskuloskeletal seperti neuropati perifer dan tendinopati Achilles pada regio pergelangan kaki. Hal ini beresiko menimbulkan efek lanjutan berupa perubahan struktur berjalan, kekakuan sendi hingga luka tukak telapak kaki. Tatalaksana tendinopati DM hingga saat ini terbatas pada pengurangan gejala lanjutan tanpa meningkatkan proses regenerasi tendon, sehingga dibutuhkan penelitian untuk menilai efek terapi dari sekretom dan eksosom SPM dalam hal perbaikan struktur tendon. Hal ini diwakili oleh penggunaan hewan coba tikus SD yang telah terinduksi menjadi tendinopati DM. Metode: Studi ini melibatkan fase studi pilot pertama, kedua, dan penelitian utama. Tikus SD diperoleh dan diberikan diet tinggi lemak (HFD) dan pemberian larutan fruktosa 55% selama delapan minggu. Diabetes diinduksi menggunakan injeksi streptozotocin (STZ) intraperitoneal berbagai dosis. Studi pilot pertama bertujuan untuk menentukan volume cairan yang dapat diinjeksikan ke area peritendon. Sementara itu, studi pilot kedua bertujuan untuk mengidentifikasi dosis STZ yang efektif. Dalam fase penelitian utama, tikus diabetes menerima injeksi lokal eksosom, sekretom, atau kombinasinya. Setelah perawatan, tikus dieutanasia, dan tendon Achilles dianalisis secara histopatologi dan imunohistokimia. Hasil dan Diskusi: Studi pilot pertama menyimpulkan bahwa 0,8 ml merupakan volume cairan optimal yang dapat diinjeksikan ke area peritendon. Sementara itu, studi pilot kedua menunjukkan bahwa setelah 8 minggu HFD, pemberian fruktosa, dan injeksi STZ, kelompok STZ 26 mg/kg memiliki kadar glukosa 220,54 ± 9,11 mg/dL, dan kelompok STZ 30mg/kg memiliki 213,88 ± 8,99 mg/dL dengan perbedaan paling signifikan dalam skor Bonar diamati di kelompok STZ 30mg/kg, hal ini menunjukkan keberhasilan induksi hewan coba. Pada penelitian utama setelah pemberian sekretom, eksosom, atau kombinasi, kadar TGF-β dan IL-6 dan skor Bonar tidak menunjukkan perbedaan signifikan antar kelompok. Analisis pasca intervensi mengungkapkan perbedaan signifikan dalam kadar IL-6 dan Col-1, dimana pada kelompok perlakuan terdapat penurunan IL-6 yang signifikan pada hari ke-14 dan peningkatan Col-1 yang signifikan pada hari ke-21 dibandingkan dengan kelompok kontrol. Kesimpulan: Penelitian ini menunjukkan bahwa kombinasi diet HFD, pemberian fruktosa, dan dosis injeksi STZ 30 mg/kg efektif menciptakan hewan model tendinopati DM. Skor Bonar yang tinggi pada kelompok STZ mengindikasikan kerusakan tendon signifikan. TGF-β dan IL-6 tidak menunjukkan perbedaan signifikan antar kelompok, namun IL-6 meningkat pada hari ke-14 dan Col-1 pada hari ke-21 pada kelompok intervensi secara signifikan, menunjukkan potensi terapi eksosom dan sekretom pada penyembuhan tendon. ......Introduction: The hyperglycemic effects and Advanced Glycation Endproduct (AGE) of diabetes mellitus (DM) are often associated with musculoskeletal complications such as peripheral neuropathy and Achilles tendinopathy in the region of the legs and ankles. It is one of the risks of developing advanced negative effects such as changes in walking structure, stiffness of the joints to ulcer wounds on the the ankle. The management of DM tendinopathy to date is limited to reducing advanced symptoms without enhancing tendon regeneration process, therefore, further research is needed to assess the therapeutic effects of MSC secretomes and exosomes in terms of tendon structure improvement. It is represented by the use of SD rats induced into DM tendinopathy. Methods: This study involves two pilot study phases and the main research. SD mice were obtained and given a high-fat diet (HFD) and given 55% fructose solution foreight weeks. Diabetes is induced by injection of streptozotocin (STZ). The first phase of the pilot study aims to determine the volume of liquid injected into the peritendon area, and the second phase aims to identify an effective dose of STZ to induce DM. In the main study, diabetic mice received local injections of exosomes, secretomes, or a combination of them. After treatment, the rats were euthanazied, and the Achilles tendon was analysed histopathologically and immunohistochemically. Results and Discussion: The first pilot study concluded that 0.8 ml was the optimal fluid volume that could be injected into the peritendon area. Meanwhile, the second pilot study showed that after 8 weeks of HFD, fructose administration, and injection of STZ, the STZ 26 mg/kg group had a glucose level of 220.54 ± 9.11 mg/dL, and the STZ 30 mg/kg group had 213.88 ± 8.99 mg/dL with the most significant difference in Bonar score was observed in the STZ 30mg/kg group, this indicates successful induction of experimental animals. In the main study after administering secretome, exosome, or a combination of the two, the levels of TGF-β and IL-6 and the Bonar score did not show significant differences between groups. Post-intervention analysis revealed significant differences in IL-6 and Col-1 levels, in which the treatment group there was a significant decrease in IL-6 on day 14 and a significant increase in Col-1 on day 21 compared to the control group. Conclusion: This study shows that a combination of HFD, fructose administration, and STZ 30mg/kg are effective in creating animal model for diabetic Achilles tendinopathy. A high Bonar score in the STZ group indicates significant tendon damage. TGF-β and IL-6 did not show significant differences between the groups, but IL-6 increased on day 14 and Col-1 on day 21 in the intervention groups significantly, indicating the potential for exosome and secretome therapy on tendon healing. Keyword: diabetic Achilles tendinopathy, Sprague Dawley rats, exosome and secretome combination, bone marrow mesenchymal stem cel