Abstract
In recent years, perivascular stem cells (PVCs) have gained increasing attention as a promising source for regenerative medicine due to their greater differentiation potential compared to multipotent mesenchymal stem cells (MSCs). It has been reported that growth differentiation factor-5 (GDF-5) is involved in regulating proliferation and chondrogenic differentiation of MSCs. In this study, we investigated the effect of GDF-5 on the proliferation and chondrogenic differentiation of PVCs isolated from human umbilical cords. The supplementation of PVC cultures with GDF-5 (100 ng/mL) significantly enhanced their proliferative rate and augmented the size of pellets in micromass pellet cultures for chondrogenic induction. Although similar expression levels of chondrogenic-related genes were observed in chondrogenic pellets treated with GDF-5 compared to the pellets without GDF-5 treatment, these results indicate that supplementation of GDF-5 is able to acquire more chondrocytes when starting with equal amount of PVCs. Our study suggests that GDF-5 is an effective agent for the enhancement of PVC proliferation, thereby achieving a higher number of chondrocytes that are applicable in therapeutic doses for cartilage regeneration.
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Harris JD, Siston RA, Pan X, Flanigan DC. Autologous chondrocyte implantation: a systematic review. J Bone Joint Surg Am 2010;92:2220–2233.
Hollander AP, Dickinson SC, Kafienah W. Stem cells and cartilage development: complexities of a simple tissue. Stem Cells 2010;28:1992–1996.
Zeifang F, Oberle D, Nierhoff C, Richter W, Moradi B, Schmitt H. Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: a randomized clinical trial. Am J Sports Med 2010;38:924–933.
Gong Y, Su K, Lau TT, Zhou R, Wang DA. Microcavitary hydrogel-mediating phase transfer cell culture for cartilage tissue engineering. Tissue Eng Part A 2010;16:3611–3622.
Han EH, Bae WC, Hsieh-Bonassera ND, Wong VW, Schumacher BL, Görtz S, et al. Shaped, stratified, scaffold-free grafts for articular cartilage defects. Clin Orthop Relat Res 2008;466:1912–1920.
Furukawa KS, Imura K, Tateishi T, Ushida T. Scaffold-free cartilage by rotational culture for tissue engineering. J Biotechnol 2008;133:134–145.
Coleman CM, Curtin C, Barry FP, O’Flatharta C, Murphy JM. Mesenchymal stem cells and osteoarthritis: remedy or accomplice? Hum Gene Ther 2010;21:1239–1250.
Saha S, Kirkham J, Wood D, Curran S, Yang XB. Informing future cartilage repair strategies: a comparative study of three different human cell types for cartilage tissue engineering. Cell Tissue Res 2013;352:495–507.
Marquass B, Schulz R, Hepp P, Zscharnack M, Aigner T, Schmidt S, et al. Matrix-associated implantation of predifferentiated mesenchymal stem cells versus articular chondrocytes: in vivo results of cartilage repair after 1 year. Am J Sports Med 2011;39:1401–1412.
Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 2008;3:301–313.
Hong SH, Maghen L, Kenigsberg S, Teichert AM, Rammeloo AW, Shlush E, et al. Ontogeny of human umbilical cord perivascular cells: molecular and fate potential changes during gestation. Stem Cells Dev 2013;22: 2425–2439.
Baksh D, Yao R, Tuan RS. Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells 2007;25:1384–1392.
Kim JH, Lee MC, Seong SC, Park KH, Lee S. Enhanced proliferation and chondrogenic differentiation of human synovium-derived stem cells expanded with basic fibroblast growth factor. Tissue Eng Part A 2011;17: 991–1002.
Murphy MK, Huey DJ, Hu JC, Athanasiou KA. TGF-ß1, GDF-5, and BMP-2 stimulation induces chondrogenesis in expanded human articular chondrocytes and marrow-derived stromal cells. Stem Cells 2015;33: 762–773.
Lee S, Kim JH, Jo CH, Seong SC, Lee JC, Lee MC. Effect of serum and growth factors on chondrogenic differentiation of synovium-derived stromal cells. Tissue Eng Part A 2009;15:3401–3415.
Liu Z, Jia C, Han C. [Experimental study on chondrogenic differentiation of rabbit adipose-derived stem cells treated with growth differentiation factor 5]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2009;23:483–489.
Feng G, Wan Y, Balian G, Laurencin CT, Li X. Adenovirus-mediated expression of growth and differentiation factor-5 promotes chondrogenesis of adipose stem cells. Growth Factors 2008;26:132–142.
Coleman CM, Tuan RS. Functional role of growth/differentiation factor 5 in chondrogenesis of limb mesenchymal cells. Mech Dev 2003;120: 823–836.
Tian HT, Zhang B, Tian Q, Liu Y, Yang SH, Shao ZW. Construction of self-assembled cartilage tissue from bone marrow mesenchymal stem cells induced by hypoxia combined with GDF-5. J Huazhong Univ Sci Technolog Med Sci 2013;33:700–706.
Coleman CM, Vaughan EE, Browe DC, Mooney E, Howard L, Barry F. Growth differentiation factor-5 enhances in vitro mesenchymal stromal cell chondrogenesis and hypertrophy. Stem Cells Dev 2013;22:1968–1976.
Sun Z, Zhang Y, Yang S, Jia J, Ye S, Chen D, et al. Growth differentiation factor 5 modulation of chondrogenesis of self-assembled constructs involves gap junction-mediated intercellular communication. Dev Growth Differ 2012;54:809–817.
Zhang B, Yang S, Sun Z, Zhang Y, Xia T, Xu W, et al. Human mesenchymal stem cells induced by growth differentiation factor 5: an improved self-assembly tissue engineering method for cartilage repair. Tissue Eng Part C Methods 2011;17:1189–1199.
Al-Sharabi N, Xue Y, Fujio M, Ueda M, Gjerde C, Mustafa K, et al. Bone marrow stromal cell paracrine factors direct osteo/odontogenic differentiation of dental pulp cells. Tissue Eng Part A 2014;20:3063–3072.
Park A, Hogan MV, Kesturu GS, James R, Balian G, Chhabra AB. Adipose- derived mesenchymal stem cells treated with growth differentiation factor-5 express tendon-specific markers. Tissue Eng Part A 2010; 16:2941–2951.
An B, Na S, Lee S, Kim WJ, Yang SR, Woo HM, et al. Non-enzymatic isolation followed by supplementation of basic fibroblast growth factor improves proliferation, clonogenic capacity and SSEA-4 expression of perivascular cells from human umbilical cord. Cell Tissue Res 2015;359:767–777.
Crisan M, Corselli M, Chen WC, Péault B. Perivascular cells for regenerative medicine. J Cell Mol Med 2012;16:2851–2860.
Tan SL, Ahmad RE, Ahmad TS, Merican AM, Abbas AA, Ng WM, et al. Effect of growth differentiation factor 5 on the proliferation and tenogenic differentiation potential of human mesenchymal stem cells in vitro. Cells Tissues Organs 2012;196:325–338.
Hatakeyama Y, Maruya Y, Hatakeyama J, Oka K, Tsuruga E, Inai T, et al. The Distinct Roles of Growth/Differentiation Factor-5 in Cell Proliferation and Odontoblast Differentiation from Dental Pulp Cells. Internet J Dent Sci 2012. Available from: URL: https://ispub.com/IJDS/10/2/14018.
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An, B., Heo, HR., Lee, S. et al. Supplementation of growth differentiation factor-5 increases proliferation and size of chondrogenic pellets of human umbilical cord-derived perivascular stem cells. Tissue Eng Regen Med 12, 181–187 (2015). https://doi.org/10.1007/s13770-015-0113-4
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DOI: https://doi.org/10.1007/s13770-015-0113-4