Influence of Adipose-Derived Mesenchymal Stromal Cell Demineralized Bone Composite on New Bone Formation in Critical Sized Cortical Bone Defects

Main Article Content

Nicole P Ehrhart Laura Chubb Elissa Flaumenhaft Carolyn Barret Yaling Shi


The relatively recent discovery that MSCs derived from various tissues will differentiate into osteoblasts in the presence of osteopromotive medium has allowed for new therapeutic opportunities in bone tissue engineering. We recently described the in vitro characteristics of a demineralized bone scaffold containing adipose-derived mesenchymal stromal cells (DBM/hMSC) harvested from human adipose tissue and demonstrated that this combination contains the three components that are considered optimal for bone repair: an osteoconductive scaffold, osteoinductive signaling proteins and osteogenic cells. The objective of this study was to compare and characterize the in vivo bone- forming activity of DBM/hMSC to that of DBM alone, hMSCs alone, cortico-cancellous isograft and human cortico-cancellous xenograft in an athymic rat model. A series of animal experiments were performed comparing new bone formation in critical-sized bone defects implanted with DBM/hMSC, DBM, hMSC, corticocancellous isograft, human cortico-cancellous bone graft or no treatment (empty defect). New bone formation was greatest in bone defects implanted with DBM/hMSC when compared with DBM alone, hMSCs alone, corticocancellous bone isograft, or human corticocancellous bone graft. Together, these data support preclinical proof-of-concept that DBM/hMSC will enhance bone formation in challenging healing environments.


Article Details

How to Cite
EHRHART, Nicole P et al. Influence of Adipose-Derived Mesenchymal Stromal Cell Demineralized Bone Composite on New Bone Formation in Critical Sized Cortical Bone Defects. Medical Research Archives, [S.l.], n. 1, jan. 2015. ISSN 2375-1924. Available at: <>. Date accessed: 22 july 2018.
Mesenchymal Stem Cells; Bone; Tissue Engineering,
Research Articles



1. Law S, Chaudhuri S. Mesenchymal stem cell and regenerative medicine: regeneration versus immunomodulatory challenges. American journal of stem cells 2013;2:22-38.

2. Ra JC, Shin IS, Kim SH, et al. Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem cells and development 2011;20:1297-1308.

3. Radtke CL, Nino-Fong R, Esparza Gonzalez BP, Stryhn H, McDuffee LA. Characterization and osteogenic potential of equine muscle tissue- and periosteal tissue- derived mesenchymal stem cells in comparison with bone marrow- and adipose tissue- derived mesenchymal stem cells. American journal of veterinary research 2013;74:790- 800.

4. Ben-David U, Mayshar Y, Benvenisty N. Large-scale analysis reveals acquisition of lineage-specific chromosomal aberrations in human adult stem cells. Cell stem cell 2011;9:97-102.

5. Di Bella C, Aldini NN, Lucarelli E, et al. Osteogenic protein-1 associated with mesenchymal stem cells promote bone allograft integration. Tissue engineering Part A 2010;16:2967-2976.

6. Jo CH, Yoon PW, Kim H, Kang KS, Yoon KS. Comparative evaluation of in vivo osteogenic differentiation of fetal and adult mesenchymal stem cell in rat critical-sized femoral defect model. Cell and tissue research 2013.

7. Bochkov NP, Voronina ES, Katosova LD, Kuleshov NP, Nikitina VA, Chausheva AI. [Genetic safety of cellular therapy]. Vestnik Rossiiskoi akademii meditsinskikh nauk
/ Rossiiskaia akademiia meditsinskikh nauk 2011:5-10.

8. Goldring CE, Duffy PA, Benvenisty N, et al. Assessing the safety of stem cell therapeutics. Cell stem cell 2011;8:618-628.

9. Shi Y, Niedzinski JR, Samaniego A, Bogdansky S, Atkinson BL. Adipose- derived stem cells combined with a demineralized cancellous bone substrate for bone regeneration. Tissue engineering Part A 2012;18:1313-1321.

10. Xu JZ, Qin H, Wang XQ, et al. Repair of large segmental bone defects using bone marrow stromal cells with demineralized bone matrix. Orthopaedic surgery 2009;1:34- 41.

11. Clokie CM, Moghadam H, Jackson MT, Sandor GK. Closure of critical sized defects with allogenic and alloplastic bone substitutes. The Journal of craniofacial surgery 2002;13:111-121; discussion 122-113.

12. Yew TL, Huang TF, Ma HL, et al. Scale-up of MSC under hypoxic conditions for allogeneic transplantation and enhancing bony regeneration in a rabbit calvarial defect model. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2012;30:1213-1220.

13. Peterson B, Zhang J, Iglesias R, et al. Healing of critically sized femoral defects, using genetically modified mesenchymal stem cells from human adipose tissue. Tissue engineering 2005;11:120-129.

14. Park KH, Kim H, Moon S, Na K. Bone morphogenic protein-2 (BMP-2) loaded nanoparticles mixed with human mesenchymal stem cell in fibrin hydrogel for bone tissue engineering. Journal of bioscience and bioengineering 2009;108:530-537.

15. Kim HJ, Kim UJ, Kim HS, et al. Bone tissue engineering with premineralized silk scaffolds. Bone 2008;42:1226-1234.

16. Kim SE, Jeon O, Lee JB, et al. Enhancement of ectopic bone formation by bone morphogenetic protein-2 delivery using heparin-conjugated PLGA nanoparticles with transplantation of bone marrow-derived mesenchymal stem cells. Journal of biomedical science 2008;15:771-777.

17. Supronowicz P, Gill E, Trujillo A, et al. Human adipose-derived side population stem cells cultured on demineralized bone matrix for bone tissue engineering. Tissue engineering Part A 2011;17:789-798.

18. Lin Y, Liu L, Li Z, et al. Pluripotency potential of human adipose-derived stem cells marked with exogenous green fluorescent protein. Molecular and cellular biochemistry 2006;291:1-10.

19. Hsu WK, Wang JC, Liu NQ, et al. Stem cells from human fat as cellular delivery vehicles in an athymic rat posterolateral spine fusion model. The Journal of bone and joint surgery American volume 2008;90:1043-1052.

20. Minamide A, Yoshida M, Kawakami M, et al. The effects of bone morphogenetic protein and basic fibroblast growth factor on cultured mesenchymal stem cells for spine fusion. Spine 2007;32:1067-1071.

21. de Girolamo L, Arrigoni E, Stanco D, et al. Role of autologous rabbit adipose- derived stem cells in the early phases of the repairing process of critical bone defects. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2011;29:100-108.

22. Lopez MJ, McIntosh KR, Spencer ND, et al. Acceleration of spinal fusion using syngeneic and allogeneic adult adipose derived stem cells in a rat model. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2009;27:366-373.

23. Arinzeh TL, Peter SJ, Archambault MP, et al. Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. The Journal of bone and joint surgery American volume 2003;85-A:1927-1935.

24. Shih HN, Shih LY, Sung TH, Chang YC. Restoration of bone defect and enhancement of bone ingrowth using partially demineralized bone matrix and marrow stromal cells. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2005;23:1293-1299.

25. Nikitina VA, Osipova EY, Katosova LD, et al. Study of genetic stability of human bone marrow multipotent mesenchymal stromal cells. Bulletin of experimental biology and medicine 2011;150:627-631.

26. Hernigou P, Poignard A, Beaujean F, Rouard H. Percutaneous autologous bone- marrow grafting for nonunions. Influence of the number and concentration of progenitor cells. The Journal of bone and joint surgery American volume 2005;87:1430-1437.

Most read articles by the same author(s)

Obs.: This plugin requires at least one statistics/report plugin to be enabled. If your statistics plugins provide more than one metric then please also select a main metric on the admin's site settings page and/or on the journal manager's settings pages.