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In Vitro Differentiation of Human Mesenchymal Stem Cells into Functional Cardiomyocyte-like Cells
Published on: August 9, 2017
Stem cell-derived cardiomyocytes after bone marrow and heart transplantation
R A de Weger1, I Verbrugge, A H Bruggink
1Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands. r.deweger@umcutrecht.nl
Insights
Stem cells from bone marrow (BM) transplantation and cardiac transplants (HTX) can differentiate into cardiomyocytes. Up to 1% of heart cells may originate from BM-derived stem cells, with similar proportions in both procedures.
Area of Science:
- Cardiovascular Biology
- Stem Cell Research
- Transplantation Medicine
Background:
- Cardiomyocytes exhibit limited regenerative capacity after injury.
- Tissue repair may involve stem cell infiltration and differentiation.
- Understanding stem cell contribution to cardiac regeneration is crucial.
Purpose of the Study:
- To investigate the influx and differentiation of stem cells into cardiomyocytes.
- To compare stem cell contribution in bone marrow transplantation (BMT) and cardiac allotransplantation (HTX).
- To determine the origin of newly formed cardiomyocytes after transplantation.
Main Methods:
- Analysis of gender-mismatched BMT (male donor to female recipient) and cardiac allotransplantation (HTX; female donor to male recipient).
- Y-chromosome in situ hybridization combined with immunohistochemical cell characterization.
- Quantification of Y-chromosome-positive cells, including cardiomyocytes, endothelial cells, and inflammatory cells.
Main Results:
- Cardiomyocytes of apparent bone marrow (BM) origin were detected in both BMT and HTX recipients.
- The proportion of BM-derived cardiomyocytes was similar in both groups, amounting to at most 1% of all cardiomyocytes.
- The number of stem cell-derived cardiomyocytes did not change significantly over time.
- Higher numbers of BM-derived cardiomyocytes correlated with increased Y-chromosome-positive inflammatory cell infiltration.
- Y-chromosome-positive endothelial cells were found in small numbers in small blood vessels.
Conclusions:
- Bone marrow-derived stem cells can differentiate into cardiomyocytes following BMT and HTX.
- The contribution of BM-derived stem cells to cardiomyocyte population is limited (≤1%) and comparable between BMT and HTX.
- Inflammatory cell infiltration may play a role in the engraftment of BM-derived stem cells in the heart.
Abstract:
Cardiomyocytes are a stable cell population with only limited potential for renewal after injury. Tissue regeneration may be due to infiltration of stem cells, which differentiate into cardiomyocytes. We have analysed the influx of stem cells in the heart of patients who received either a gender-mismatched BMT (male donor to female recipient) or a gender-mismatched cardiac transplant (HTX; female donor to male recipient). The proportion of infiltrating cells was determined by Y-chromosome in situ hybridization combined with immunohistochemical cell characterization. In BM transplanted patients and in cardiac allotransplant recipients, cardiomyocytes of apparent BM origin were detected. The proportions were similar in both groups and amounted up to 1% of all cardiomyocytes. The number of stem cell-derived cardiomyocytes did not alter significantly in time, but were relatively high in cases where large numbers of BM-derived Y-chromosome-positive infiltrating inflammatory cells were present. The number of Y-chromosome-positive endothelial cells was small and present only in small blood vessels. The number of BM-derived cardiomyocytes in both BMT and HTX is not significantly different between the two types of transplantation and is at most 1%.
