PMID- 24166198 OWN - NLM STAT- MEDLINE DCOM- 20140926 LR - 20211021 IS - 1573-4919 (Electronic) IS - 0300-8177 (Linking) VI - 387 IP - 1-2 DP - 2014 Feb TI - Cotransplantation of human umbilical cord-derived mesenchymal stem cells and umbilical cord blood-derived CD34(+) cells in a rabbit model of myocardial infarction. PG - 91-100 LID - 10.1007/s11010-013-1874-5 [doi] AB - The objective of the study is to investigate the effect of hypoxic preconditioning on the immunomodulatory properties of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and the effect of cotransplantation of hUC-MSCs and human umbilical cord blood (hUCB)-derived CD34(+) cells in a rabbit model of myocardial infarction. hUC-MSCs with or without hypoxic preconditioning by cobalt chloride were plated in a 24-well plate, and then cocultured with hUCB-CD34(+) cells and PBMCs for 96 h at 37 degrees C in a 5% CO(2) incubator. For the negative control, hUC-MSCs were omitted. The groups were divided as follows: A1 = HP-MSCs + hUCB-CD34(+) cells + PBMC, A2 = hUC-MSCs + hUCB-CD34(+) cells + PBMC, Negative Control = hUCB-CD34(+) cells + PBMC. Culture supernatants of each group were collected, and the IL-10 and IFN-gamma levels were measured by ELISA. A rabbit model of MI was established using a modified Fujita method. The animals were then randomized into three groups and received intramyocardial injections of 0.4 ml of PBS alone (n = 8, PBS group), hUC-MSCs in PBS (n = 8, hUC-MSCs group), or hUC-MSCs + CD34(+) cells in PBS (n = 8, Cotrans group), at four points in the infarct border zone. Echocardiography was performed at baseline, 4 weeks after MI induction, and 4 weeks after cell transplantation, respectively. Stem cell differentiation and neovascularization in the infracted area were characterized for the presence of cardiac Troponin I (cTnI) and CD31 by immunohistochemical staining, and the extent of myocardial fibrosis was evaluated by hematoxylin and eosin (H&E) and Masson's trichrome. IFN-gamma was 27.00 +/- 1.11, 14.20 +/- 0.81, and 7.22 +/- 0.14 pg/ml, and IL-10 was 31.68 +/- 3.08, 61.42 +/- 1.08, and 85.85 +/- 1.80 pg/ml for the Control, A1 and A2 groups, respectively, which indicated that hUCB-CD34(+) cells induced immune reaction of peripheral blood mononuclear cells, whereas both hUC-MSCs and HP-MSCs showed an immunosuppressive effect, which, however, was attenuated by hypoxic preconditioning. The Cotrans group had less collagen deposition in the infarcted myocardium and better heart function than the hUC-MSCs or PBS group. The presence of cTnI-positive cells and CD31-positive tubular structures indicated the differentiation of stem cells into cardiomyocytes and neovascularization. The microvessel density was 12.19 +/- 3.05/HP for the hUC-MSCs group and 31.63 +/- 2.45/HP for the Cotrans group, respectively (P < 0.01). As a conclusion, both hUC-MSCs and HP-MSCs have an immunosuppressive effect on lymphocytes, which, however, can be attenuated by hypoxic preconditioning. Cotransplantation of hUC-MSCs and hUCB-CD34(+) cells can improve heart function and decrease collagen deposition in post-MI rabbits. Thus, a combined regimen of hUC-MSCs and hUCB-CD34(+) cells would be more desirable than either cells administered alone. This is most likely due to the increase of cardiomyocytes and enhanced angiogenesis in the infarcted myocardium. FAU - Li, Tong AU - Li T AD - Tianjin Third Central Hospital, Tianjin, China, litong3zx@sina.com. FAU - Ma, Qunxing AU - Ma Q FAU - Ning, Meng AU - Ning M FAU - Zhao, Yue AU - Zhao Y FAU - Hou, Yuelong AU - Hou Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131029 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Antigens, CD34) SB - IM MH - Animals MH - Antigens, CD34/metabolism MH - Cells, Cultured MH - *Cord Blood Stem Cell Transplantation MH - Coronary Vessels/physiopathology MH - Female MH - Humans MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/metabolism MH - Myocardial Infarction/*therapy MH - Myocardium/pathology MH - Rabbits MH - Ventricular Function, Left EDAT- 2013/10/30 06:00 MHDA- 2014/09/27 06:00 CRDT- 2013/10/30 06:00 PHST- 2013/07/29 00:00 [received] PHST- 2013/10/18 00:00 [accepted] PHST- 2013/10/30 06:00 [entrez] PHST- 2013/10/30 06:00 [pubmed] PHST- 2014/09/27 06:00 [medline] AID - 10.1007/s11010-013-1874-5 [doi] PST - ppublish SO - Mol Cell Biochem. 2014 Feb;387(1-2):91-100. doi: 10.1007/s11010-013-1874-5. Epub 2013 Oct 29.