Doctoral Studies in Medical Sciences: Intravenous Administration of Adipose-Derived Mesenchymal Stem Cells Promises New Therapy for Osteoporosis

Located in the Hall Room Lt.III, Postgraduate Building, Udayana University, Denpasar, a Doctoral Promotion examination was held with Promovenda candidate Dr. Nadia Permatasari, M.Biomed (AAM) with the dissertation title "Intravenous Administration of Adipose-Derived Mesenchymal Stem Cells Produces Osteoprotegerin Levels, Transforming Growth Factor Beta 1 Expression, and Higher Osteoblast Cell Counts, Lower Osteoclast Cell Counts in Ovariectomized Female Wistar Rats (Rattus Norvegicus)" (1/4/2024).


Osteoporosis is a serious clinical condition that can reduce quality of life and the number is increasing along with increasing life expectancy. The obstacle to osteoporosis management at this time is that there is still no regenerative therapy that has proven effective for the treatment of osteoporosis. 


Adipose-derived Mesenchymal Stem Cell (AdMSC) secretes osteoprotegerin (OPG) and Transforming Growth Factor-β1 (TGF-1) in in vitro studies that can inhibit osteoclastogenesis and promote osteoclast apoptosis. AdMSC can also differentiate into osteogenic lineage into osteoblasts, which will secrete OPG and Receptor Activator NF-κB (RANK) Ligand (RANKL) so that osteoclastogenesis can be inhibited. The purpose of this study was to prove that intravenous administration of AdMSCs resulted in higher levels of OPG, TGF-1 expression, and higher number of osteoblast cells, lower number of osteoclast cells in ovariectomized wistar strain female rats (Rattus norvegicus).


This study used a true experimental study design with a randomized post test only control group design using 36 Wistar rats which were divided into 2 groups, namely 18 rats in the control group and 18 rats in the treatment group. The control group was given intravenous distilled water and the treatment group was given intravenous AdMSC 2x106 cells/kgBB. The examination techniques used were histopathology, Enzyme-Linked Immunosorbent Assay (ELISA), and immunohistochemistry (IHC).


This study showed significantly higher OPG levels (2.75 ± 1.07, p < 0.001), TGF-β1 expression (3.57 ± 1.05, p < 0.001), and osteoblast cell count (5.35 ± 1.58, p < 0.001) in the treatment group, significantly lower osteoclast cell count (1.20 ± 0.65, p < 0.001) in the treatment group than the control group.


This study proves that intravenous administration of AdMSCs produces significantly higher levels of OPG, TGF-β1 expression, and number of osteoblast cells, significantly lower number of osteoclast cells in ovariectomized female wistar strain rats (Rattus norvegicus) by inhibiting osteoclastogenesis, increasing osteoclast apoptosis, and osteogenic differentiation into osteoblast cells so that intravenous AdMSCs can be used as a theoretical basis for clinical trials on regenerative therapy for osteoporosis treatment.


This examination was chaired by the Dean of FK Unud Prof.Dr.dr. Komang Januartha Putra Pinatih, M.Kes, with a team of examiners:

1. Prof. Dr. dr. Wimpie I Pangkahila, Sp.And.SubspecSAAM (Promoter)

2. Prof. Dr. dr. I Ketut Suyasa, Sp.B., Sp.OT(K) (Copromoter I)

3. Prof. Dr. dr. I Made Bakta, Sp.PD-KHOM (Copromoter II)

4. Prof. Dr. dr. I Made Jawi, M.Kes

5. Prof. Dr. Ir. Ida Bagus Putra Manuaba, M.Phil

6. Prof. Dr. dr. Ketut Siki Kawiyana, Sp.B., Sp.OT(K)

7. Prof. Dr. dr. Bagus Komang Satriyasa, M.Repro

8. Prof. dr. I Made Ady Wirawan, S.Ked, MPH, Ph.D.

9. Dr. dr. I Nyoman Semadi, Sp.B., Sp.BTKV(K)

10. Dr. dr. Desak Made Wihandani, M.Kes


While academic invitations are :

1. Dr. dr. Luh Putu Ratna Sundari, M.Biomed

2. Dr. dr. I Gusti Putu Suka Aryana, Sp.PD,K-Ger,FINASIM

3. Dr. dr. Made Bramantya Karna, Sp.OT(K)

4. Dr. dr. I Gusti Ngurah Wien Aryana, Sp.OT(K)

5. dr. Made Winarsa Ruma, S.Ked., Ph.D


In this exam, Dr. dr. Nadia Permatasari, M.Biomed (AAM), passed as the 413th Doctoral Graduate of the Doctor Degree of Medical Sciences Study Program with a very satisfying predicate.