PMID- 26222206 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20220409 IS - 1095-8355 (Electronic) IS - 1065-6995 (Linking) VI - 40 IP - 1 DP - 2016 Jan TI - Enhancement of angiogenic effects by hypoxia-preconditioned human umbilical cord-derived mesenchymal stem cells in a mouse model of hindlimb ischemia. PG - 27-35 LID - 10.1002/cbin.10519 [doi] AB - It has been studied that mesenchymal stem cells (MSCs) have the capability to promote angiogenesis. Furthermore, there is strong evidence that hypoxic conditions can enhance angiogenesis and immune modulation mediated by MSCs, a notion that has been applied in many fields of clinical application. In the present study, we compared the efficacy of hypoxia preconditioned human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and normoxia conditioned hUC-MSCs for the treatment of ischemic injury in hindlimbs of an immunodeficient mouse model. Expression of negative markers for MSC such as CD31, CD34, and CD45 or positive markers such as CD44, CD73, CD90, and CD105 was not significantly changed in hypoxia preconditioned hUC-MSCs compared with hUC-MSCs cultured in normoxic condition. Expression of angiogenesis-related genes such as COX-2, VEGF, Tie-2, and TGF-beta1 was increased compared with hUC-MSCs cultured in normoxic conditions. In the in vivo model, CD31 expression as a marker of angiogenesis was significantly increased in the ischemic limbs at 1 month after injection with hypoxic hUC-MSCs. Angiogenesis-related genes such as Ang-1, COX-1, PIGF, and MCP-1 were significantly upregulated in the muscle of ischemic hindlimbs treated with hypoxic hUC-MSCs than normoxic hUC-MSCs. Expression of proinflammatory genes such as IL-1, and IL-20 was reduced, whereas TGF-beta1, which has an anti-inflammatory effect, was strongly increased. In conclusion, hypoxic culture conditions could induce expression of angiogenesis related genes in hUC-MSCs, and hypoxia preconditioned hUC-MSCs showed enhancing effects by inducing angiogenesis and low inflammatory immune response compared with normoxic hUC-MSCs in the ischemia injured hindlimb of immunodeficient mice. CI - (c) 2015 International Federation for Cell Biology. FAU - Han, Kyu-Hyun AU - Han KH AD - Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. FAU - Kim, Ae-Kyeong AU - Kim AK AD - Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. FAU - Kim, Min-Hee AU - Kim MH AD - Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. FAU - Kim, Do-Hyung AU - Kim DH AD - Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. FAU - Go, Ha-Nl AU - Go HN AD - Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. FAU - Kim, Dong-Ik AU - Kim DI AD - Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150817 PL - England TA - Cell Biol Int JT - Cell biology international JID - 9307129 RN - 0 (Angiogenesis Inducing Agents) RN - 0 (Interleukins) RN - 0 (Transforming Growth Factor beta1) RN - U91R7IMG8U (interleukin 20) SB - IM MH - Angiogenesis Inducing Agents/*metabolism MH - Animals MH - Cell Differentiation/physiology MH - Cell Hypoxia/physiology MH - Cells, Cultured MH - Disease Models, Animal MH - Hindlimb/*blood supply MH - Humans MH - Interleukins/metabolism MH - Ischemia/*therapy MH - Male MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/*cytology/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Transforming Growth Factor beta1/metabolism MH - Umbilical Cord/cytology OTO - NOTNLM OT - angiogenesis OT - hypoxia OT - immunodeficient OT - inflammatory OT - mesenchymal stem cell (MSC) OT - normoxia EDAT- 2015/07/30 06:00 MHDA- 2016/12/15 06:00 CRDT- 2015/07/30 06:00 PHST- 2015/07/03 00:00 [received] PHST- 2015/07/26 00:00 [accepted] PHST- 2015/07/30 06:00 [entrez] PHST- 2015/07/30 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] AID - 10.1002/cbin.10519 [doi] PST - ppublish SO - Cell Biol Int. 2016 Jan;40(1):27-35. doi: 10.1002/cbin.10519. Epub 2015 Aug 17.