Published: 2017-01-16

Effect of adipose derived stem cells on ovariectomised Wistar rats

Anitha Oommen, Ibrahim Hassan Al-Zahrani


Background: Various clinical trials are going to determine the efficacy of human Adipose Derived Stem Cells (hADSCs) in the treatment of degenerative diseases including osteoporosis. Stem cell therapy for osteoporosis is aimed at inducing new bone formation by the proliferation and differentiation of bone progenitor cells. The therapeutic potential of hADSCs has to be investigated in animal models of osteoporosis before suggesting it as a therapeutic option.

Methods: hADSCs were cultured in the Dulbecco’s Modified Eagle’s Medium (DMEM) supplemented with 4 mM L-glutamine and 110 mg/l sodium pyruvate, 10% Fetal Bovine Serum (FBS), 1% penicillin–streptomycin and non-essential amino acids. For osteogenic differentiation of hADSCs, cells were cultured as above then were exposed to osteogenic induction medium for seven days. Intravenous infusion of osteogenesis induced hADSCs was given to 20 ovariectomised Wistar rats three months after ovariectomy (test group) and 20 ovariectomised rats were kept as controls. Rats were sacrificed 35 days after infusion and tibial cross sections at the level of tibio-fibular joint were stained with H&E & Masson’s trichrome. The digital slide images were viewed using Aperio Image Scope software.

Results: The results showed that there was new bone formation in the test group, indicated by osteoid formation and osteoblasts. There was significant increase in the cortical thickness in the test group when compared with the control group. There was no significant increase in trabecular volume when compared to the control group.

Conclusions: hADSCs after osteogenic induction may have the potential to enhance new bone formation and may be useful in the treatment of osteoporosis.



Adipose derived stem cells, Female wistar rats, Osteoporosis, New bone formation

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Mimeault M, Batra SK. Recent progression tissue-resident adult stem cell biology and their therapeutic implications. Stem Cell Rev. 2008;4:27-49.

Mimeault M, Batra SK. Concise review: recent advances on the significance of stem cells in tissue regeneration and cancer therapies. Stem Cells. 2006;24:2319-45.

Gimble JM, Katz AJ, Bunnell BA. Adipose-derived stem cells for regenerative medicine. Circ Res. 2007;100:1249-60.

Guan M, Yao W, Liu R, Lam KS, Nolta J, Jia J, et al. Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass. Nat Med. 2012;18:456-62.

Jung Y, Bauer G, Nolta JA. Concise review: induced pluripotent stem cell-derived mesenchymal stem cells: progress toward safe clinical products. Stem Cells. 2012;30:42-7.

Stappenbeck TS, Miyoshi H. The role of stromal stem cells in tissue regeneration and wound repair. Science. 2009;324(5935):1666-9.

Guillot PV, Abass O, Bassett JH, Shefelbine SJ, Bou-Gharios G, Chan J, et al. Intrauterine transplantation of human fetal mesenchymal stem cells from first-trimester blood repairs bone and reduces fractures in osteogenesis imperfect mice. Blood. 2008;1(111):1717-25.

Hanaa HA, El-sayed M, El-sayed MYB, Shousha WGH, Rashed LA, Abdo SM. Potential role of bone marrow derived mesenchymal stem cells with or without injectable calcium phosphate composite in management of osteoporosis in rat model. Int J Pharm Pharmaceut Sci. 2013;5:494-504.

Ogawa R, Mizuno H, Hyakusoku H, Watanabe A. Chondrogenic and osteogenic differentiation of adipose-derived stem cells isolated from GFP transgenic mice. J Nippon Med Sch. 2004;71:240-1.

Hietala EL. The effect of ovariectomy on periosteal bone formation and bone resorption in adult rats. Bone Miner. 1993;20:57-65.

Ra JC, Shin IS, Kim SH, Kang SK, Kang BC, Lee HY, et al. Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem Cell Dev. 2011;20(8):1297-308.

Brouwers JEM, Van Rietbergen B, Huiskes R. Effects of PTH treatment on tibial bone of ovariectomized rats assessed by in vivo micro-CT. Osteoporos Int. 2009;22(11):1823-35.

Zhang W, Kanchara M, Zhang Y, Wang X, Ishida T. β-Blocker and other analogous treatments that affect bone mass and sympathetic nerve activity in ovariectomized rats. Am J Chin Med. 2007;35:89-101.

Sang-HS, Young-PY, Hak-JK. Bone formation in a rat tibial defect model using carboxymethyl cellulose/BIOC/bone morphogenic protein-2 hybrid materials. Biomed Res Int. 2014;2014:230152.

Naim, Magda MN. Histological assessment of zoledronic acid (Aclasta) in protection against induced osteoporosis in female albino rats. Egypt J Histol. 2011;34(1):129-38.

Katavic V, Lukic IK, Kovacic N, Grcevic D, Joseph A, Lorenzo, et al. Increased bone mass is a part of the generalized lymphoproliferative disorder phenotype in the mouse 1, 2. J Immunol. 2003;170:1540-7.

Turner AS. Animal models of osteoporosis--necessity and limitations. Eur Cell Mater. 2001;22(1):66-81.

Shuid A, Mohamad S, Mohamed N, Mokhtar S, Muhammad N, Soelaiman IM. Bone oxidative changes during early fracture healing of postmenopausal osteoporosis rat model. Asian J Animal Veterin Adv. 2011;6:1193-203.

Jee WSS, Yao W. Overview: animal models of osteopenia and osteoporosis. J Musculoskelet Neuronal Interact. 2001;1:193-207.

Lelovas PP, Xanthos TT, Thoma SE, Lyritis GP, Dontas IA. The laboratory rat as an animal model for osteoporosis research. Comp Med. 2008;58:424-30.

Lim JY, Ra JC, Shin IS, Jang YH, An HY, Choi JS, et al. Systemic transplantation of human adipose tissue-derived mesenchymal stem cells for the regeneration of irradiation-induced salivary gland damage. PLoS One. 2013;8(8):e71167.

Sun CK ,Chang CL, Lin YC, Kao YH, Chang LT, Yen CH, et al. Systemic administration of autologous adipose-derived mesenchymal stem cells alleviates hepatic ischemia-reperfusion injury in rats. Crit Care Med. 2012;40(4):1279-90.

Tajiri N, Acosta SA, Shahaduzzaman M, Ishikawa H, Shinozuka K, Pabon M, et al. Intravenous transplants of human adipose-derived stem cell protect the brain from traumatic brain injury-induced neurodegeneration and motor and cognitive impairments: cell graft biodistribution and soluble factors in young and aged rats. J Neurosci. 2014;34:313-26.

Wang YL, Li G, Zou XF, Chen XB, Shen ZY. Effect of autologous adipose-derived stem cells in renal cold ischemia and reperfusion injury. Transplant Proc. 2013;45:3198-202.

Yao W, Guan M, Jia J, Dai W, Lay YE, Amugongo S, et al. Reversing bone loss by directing mesenchymal stem cells to the bone. Stem Cells. 2013;31:2003-14.

Jeong JH, Park J, Jin ES, Min JK, Jeon SR, Kim DK. Adipose tissue-derived stem cells in the ovariectomy-induced postmenopausal osteoporosis rat model. Tissue Engin Regenerat Med. 2015;12:28-36.

Wronski TJ, Cintrón M, Dann LM. Temporal relationship between bone loss and increased bone turnover in ovariectomized rats. Calcif Tissue Int. 1988;43:179-83.

Veronesi F, Torricelli P, Borsari V, Tschon M, Rimondini L, Fini M. Mesenchymal stem cells in the aging and osteoporotic population. Crit Rev TM Eukaryot Gene Expres. 2011;21:363-77.

Pham PV. Adipose stem cells in the clinic. Biomed Res Ther. 2014;1:57-70.

Gasser JA. Stem cells in the treatment of osteoporosis. Eur Cells Materials. 2003;6:21.

Kim MG, Jung IK, Shin SH, Kim CH, Kim BJ, Kim JH, et al. Effect of adipose-derived stem cells on bone healing on titanium implant in tibia of diabetes mellitus induced rats. J Korean Assoc Oral Maxillofac Surg. 2010;36:392-401.

Carolina AM, David WD. Bone histomorphometry: a concise review for endocrinologists and clinicians. Arq Bras Endocrinol Metab. 2010;54(2):87-98.

Tao H, Yu MC, Yang HY. Effect of allogenic adipose-derived stem cell transplantation on bone mass in rats with glucocorticoid-induced osteoporosis. Nan Fang Yi Ke Da Xue Xue Bao. 2011;31:817-21.

Je HJ, JuRi P, Eun-Sun J. Adipose tissue-derived stem cells in the ovariectomy-induced postmenopausal osteoporosis rat model. Tissue Engin Regenerat Med. 2015;12:28-36.

Afshan AC, Mariano CM, John FA. Differential effects of growth hormone and Alfa calcidol on trabecular and cortical bones in hypophysectomized rats. Pediatr Res. 2009;65:403-8.

Nancy EL, Wei Y, John HK. Both hPTH(1-34) and bFGF increase trabecular bone mass in osteopenic rats but they have different effects on trabecular bone architecture. J Bone Mineral Res. 2003;s18(12):2105-15.