PMID- 28482145 OWN - NLM STAT- MEDLINE DCOM- 20191009 LR - 20191010 IS - 1932-7005 (Electronic) IS - 1932-6254 (Linking) VI - 12 IP - 2 DP - 2018 Feb TI - A controlled release system for simultaneous delivery of three human perivascular stem cell-derived factors for tissue repair and regeneration. PG - e1164-e1172 LID - 10.1002/term.2451 [doi] AB - Transplanted stem/progenitor cells improve tissue healing and regeneration anatomically and functionally, mostly due to their secreted trophic factors. However, harsh conditions at the site of injury, including hypoxia, oxidative and inflammatory stress, increased fibrosis and insufficient angiogenesis, and in some cases immunological response or incompatibility, are detrimental to stem cell survival. To overcome the complexity and deficiencies of stem cell therapy, the coacervate delivery platform is deemed promising because it offers controlled and sustained release using heparin to recapitulate the binding and stabilization of extracellular proteins by heparan sulphates in native tissues. Here we show that recombinant alternatives of three key factors [vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6)], commonly produced by perivascular stem cells under various stress conditions, can be successfully incorporated into a heparin-based coacervate. We characterized the release profile of the triply incorporated factors from the complex coacervate. The coacervate-released factors were able to exert their desired biological activities in vitro: VEGF stimulated human umbilical vein endothelial cell proliferation, MCP-1 elevated macrophage migration and IL-6 increased IgM production by IL-6-dependent cell line. Thus, a controlled release system can be used for simultaneous delivery of three stem cell-derived factors and could be useful for tissue repair and regenerative medicine. CI - Copyright (c) 2017 John Wiley & Sons, Ltd. FAU - Mansurov, Nurlan AU - Mansurov N AD - Department of Biomedical Sciences, Nazarbayev University School of Medicine, Nazarbayev University, Astana, Kazakhstan. FAU - Chen, William C W AU - Chen WCW AD - Research Laboratory of Electronics and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. FAU - Awada, Hassan AU - Awada H AD - Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA. AD - McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA. FAU - Huard, Johnny AU - Huard J AD - Department of Orthopedic Surgery and Center for Tissue Engineering and Aging Research, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USA. AD - Center for Sports Regenerative Medicine, Steadman Philippon Research Institute, Vail, CO, USA. FAU - Wang, Yadong AU - Wang Y AD - Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA. AD - McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA. FAU - Saparov, Arman AU - Saparov A AUID- ORCID: 0000-0002-4407-1236 AD - Department of Biomedical Sciences, Nazarbayev University School of Medicine, Nazarbayev University, Astana, Kazakhstan. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20170720 PL - England TA - J Tissue Eng Regen Med JT - Journal of tissue engineering and regenerative medicine JID - 101308490 RN - 0 (Chemokine CCL2) RN - 0 (Delayed-Action Preparations) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Interleukin-6) RN - 0 (Vascular Endothelial Growth Factor A) RN - 9005-49-6 (Heparin) SB - IM MH - Animals MH - Blood Vessels/*cytology MH - Cell Line MH - Chemokine CCL2/pharmacology MH - Delayed-Action Preparations/*pharmacology MH - *Drug Delivery Systems MH - Heparin/pharmacology MH - Human Umbilical Vein Endothelial Cells/cytology/drug effects/metabolism MH - Humans MH - Intercellular Signaling Peptides and Proteins/*pharmacology MH - Interleukin-6/pharmacology MH - Mice MH - RAW 264.7 Cells MH - Regeneration/*drug effects MH - Stem Cells/*metabolism MH - Vascular Endothelial Growth Factor A/pharmacology MH - Wound Healing/*drug effects OTO - NOTNLM OT - biomaterials OT - stem cells OT - tissue repair and regenerative medicine EDAT- 2017/05/10 06:00 MHDA- 2019/10/11 06:00 CRDT- 2017/05/09 06:00 PHST- 2016/08/22 00:00 [received] PHST- 2017/01/17 00:00 [revised] PHST- 2017/05/04 00:00 [accepted] PHST- 2017/05/10 06:00 [pubmed] PHST- 2019/10/11 06:00 [medline] PHST- 2017/05/09 06:00 [entrez] AID - 10.1002/term.2451 [doi] PST - ppublish SO - J Tissue Eng Regen Med. 2018 Feb;12(2):e1164-e1172. doi: 10.1002/term.2451. Epub 2017 Jul 20.