PMID- 27074878 OWN - NLM STAT- MEDLINE DCOM- 20180501 LR - 20211025 IS - 1932-7005 (Electronic) IS - 1932-6254 (Linking) VI - 11 IP - 8 DP - 2017 Aug TI - Combined treatment with platelet-rich plasma and insulin favours chondrogenic and osteogenic differentiation of human adipose-derived stem cells in three-dimensional collagen scaffolds. PG - 2398-2410 LID - 10.1002/term.2139 [doi] AB - Osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis and progressive joint destruction. Bioengineered scaffolds are widely studied for regenerative surgery strategies in osteochondral defect management, also combining the use of stem cells, growth factors and hormones. The utility in tissue engineering of human adipose-derived stem cells (ASCs) isolated from adipose tissue has been widely noted. Autologous platelet-rich plasma (PRP) represents an alternative strategy in regenerative medicine for the local release of endogenous growth factors and hormones. Here we compared the effects of three-dimensional (3D) collagen type I scaffold culture and combined treatment with PRP and human recombinant insulin on the chondro-/osteogenic differentiation of ASCs. Histochemical and biomolecular analyses demonstrated that chondro-/osteogenic differentiation was increased in ASC-populated 3D collagen scaffolds compared with two-dimensional (2D) plastic dish culture. Chondro-/osteogenic differentiation was further enhanced in the presence of combined PRP (5% v/v) and insulin (100 nm) treatment. In addition, chondro-/osteogenic differentiation associated with the contraction of ASC-populated 3D collagen scaffold and increased beta1/beta3-integrin expression. Inhibition studies demonstrated that PRP/insulin-induced chondro-/osteogenic differentiation is independent of insulin-like growth factor 1 receptor (IGF-1R) and mammalian target of rapamycin (mTOR) signalling; IGF-R1/mTOR inhibition even enhanced ASC chondro-/osteogenic differentiation. Our findings underline that 3D collagen scaffold culture in association with platelet-derived growth factors and insulin favour the chondro-/osteogenic differentiation of ASCs, suggesting new translational applications in regenerative medicine for the management of osteochondral defects. Copyright (c) 2016 John Wiley & Sons, Ltd. CI - Copyright (c) 2016 John Wiley & Sons, Ltd. FAU - Scioli, Maria Giovanna AU - Scioli MG AD - Institute of Anatomical Pathology, Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy. FAU - Bielli, Alessandra AU - Bielli A AD - Institute of Anatomical Pathology, Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy. FAU - Gentile, Pietro AU - Gentile P AD - Plastic and Reconstructive Surgery, Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy. FAU - Cervelli, Valerio AU - Cervelli V AD - Plastic and Reconstructive Surgery, Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy. FAU - Orlandi, Augusto AU - Orlandi A AD - Institute of Anatomical Pathology, Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160414 PL - England TA - J Tissue Eng Regen Med JT - Journal of tissue engineering and regenerative medicine JID - 101308490 RN - 0 (Insulin) RN - 9007-34-5 (Collagen) SB - IM MH - Adipose Tissue/cytology/*metabolism MH - Cell Differentiation/*drug effects MH - Cells, Cultured MH - Chondrogenesis/*drug effects MH - Collagen/*chemistry MH - Humans MH - Insulin/chemistry/*pharmacology MH - Osteogenesis/*drug effects MH - Platelet-Rich Plasma/*chemistry MH - Stem Cells/cytology/*metabolism MH - Tissue Scaffolds/*chemistry OTO - NOTNLM OT - IGF-1R/mTOR signalling OT - chondrogenesis/osteogenesis OT - collagen gel scaffold OT - human adipose-derived stem cells OT - insulin OT - platelet-rich plasma EDAT- 2016/04/15 06:00 MHDA- 2018/05/02 06:00 CRDT- 2016/04/15 06:00 PHST- 2015/06/26 00:00 [received] PHST- 2015/11/18 00:00 [revised] PHST- 2015/12/10 00:00 [accepted] PHST- 2016/04/15 06:00 [pubmed] PHST- 2018/05/02 06:00 [medline] PHST- 2016/04/15 06:00 [entrez] AID - 10.1002/term.2139 [doi] PST - ppublish SO - J Tissue Eng Regen Med. 2017 Aug;11(8):2398-2410. doi: 10.1002/term.2139. Epub 2016 Apr 14.