Dataset Information

Can mesenchymal stem cells induce tolerance to cotransplanted human embryonic stem cells?

ABSTRACT: Mesenchymal stem cells (MSCs) are reported to be immune privileged. We assessed whether their transplantation (Tx) could create a suppressive microenvironment mitigating rejection of coinjected human embryonic stem cells (hESCs). Three weeks after ligation-induced myocardial infarction, 40 immunocompetent rats received 150 microl of cardiac-specified hESCs (5 x 10(6)), MSCs (5 x 10(6)), hESC + MSC (5 x 10(6) for each), or control medium. Two months after Tx, left ventricle (LV) function was assessed by echocardiography, and hearts were processed for the detection of human cells by immunostaining and quantitative RT-PCR, patterns of rejection, fibrosis, and angiogenesis. Two months after Tx, LV ejection fraction (LVEF) was significantly higher in the ESC and ESC + MSC groups compared with controls. There were few engrafted cells, which expressed markers of endothelial, smooth muscle, and ventricular cardiac cells, particularly in the MSC group. Hearts of all groups demonstrated a similar infiltration by CD4(+) and CD3(+) cells but MSC-Tx resulted in a greater infiltration of FoxP3 compared with the control and ESC-alone groups. No teratoma was observed. Thus, cotransplantation of ESCs and MSCs provided better functional preservation compared with single-cell treatment alone. However, there was only modest evidence for an immunosuppressive effect of coinjected MSCs and their beneficial effects seemed rather mediated by trophic effects on the host tissue.

SUBMITTER: Puymirat E

PROVIDER: S-EPMC2834983 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Can mesenchymal stem cells induce tolerance to cotransplanted human embryonic stem cells?

Puymirat Etienne E Geha Raghed R Tomescot André A Bellamy Valérie V Larghero Jérôme J Trinquart Ludovic L Bruneval Patrick P Desnos Michel M Hagège Albert A Pucéat Michel M Menasché Philippe P

Molecular therapy : the journal of the American Society of Gene Therapy 20081007 1

Mesenchymal stem cells (MSCs) are reported to be immune privileged. We assessed whether their transplantation (Tx) could create a suppressive microenvironment mitigating rejection of coinjected human embryonic stem cells (hESCs). Three weeks after ligation-induced myocardial infarction, 40 immunocompetent rats received 150 microl of cardiac-specified hESCs (5 x 10(6)), MSCs (5 x 10(6)), hESC + MSC (5 x 10(6) for each), or control medium. Two months after Tx, left ventricle (LV) function was asse ...[more]

PMID: 18841094

Similar Datasets

Project description:Derivation of bone forming cells (osteoblasts) from human embryonic stem cells (hESCs) is a prerequisite for their use in clinical applications. However, there is no standard protocol for differentiating hESCs into osteoblastic cells. The aim of this study was to identify the emergence of a human stromal (mesenchymal and skeletal) stem cell (hMSC)-like population, known to be osteoblastic cell precursors and to test their osteoblastic differentiation capacity in ex vivo cultures and in vivo. We cultured hESCs in a feeder-free environment using serum replacement and as suspension aggregates (embryoid bodies; hEBs). Over a 20 day developmental period, the hEBs demonstrated increasing enrichment for cells expressing hMSC markers: CD29, CD44, CD63, CD56, CD71, CD73, CD105, CD106, and CD166 as revealed by immunohistochemical staining and flow cytometry (fluorescence-activated cell sorting) analysis. Ex vivo differentiation of hEBs using bone morphogenic protein 2 (BMP2) combined with standard osteoblast induction medium led to weak osteoblastic induction. Conversely, subcutaneous in vivo implantation of day 20 hEBs in immune deficient mice, mixed with hydroxyapatite/tricalcium phosphate (HA/TCP) as an osteoconductive scaffold, revealed bone and cartilage, and fibrous tissue elements after 8 weeks. These tissues were of human origin and there was no evidence of differentiation to nonmesodermal tissues. hEBs implanted in the absence of HA/TCP formed vacuolated tissue containing glandular, fibrous and muscle-like tissue elements. Conversely, implantation of undifferentiated hESCs resulted in the formation of a teratoma containing a mixture of endodermal, mesodermal, and ectodermal tissues. Our study demonstrates that hMSC-like cells can be obtained from hESCs and they can be induced to form skeletal tissues in vivo when combined with HA/TCP. These findings are relevant for tissue engineering and suggest that differentiated hEBs can provide an unlimited source for functional osteogenic cells.

Dataset Information

Can mesenchymal stem cells induce tolerance to cotransplanted human embryonic stem cells?

Publications

Can mesenchymal stem cells induce tolerance to cotransplanted human embryonic stem cells?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets