"Treg play a critical role in immune tolerance," Dr. Azevedo said. "In stem cell transplantation to treat leukemia and other blood diseases, for example, lower Treg counts are associated with the development of chronic graft-versus-host disease. However, Treg are very scarce. Finding alternative sources of stable Treg induction might produce a large enough number for effective treatment uses."
Mesenchymal stromal cells (MSCs) have been suggested as one way to achieve this. These multipotent progenitor cells, which can be isolated from a wide range of adult and postnatal tissues, are able to differentiate into diverse cell types. And like Treg, MSCs constitute an important immunoregulatory population by inhibiting both innate and adaptive immune responses.
"But thus far, the potential of MSC to recruit Treg has been poorly understood," Dr. Azevedo said.
Previous studies suggest that MSC-mediated immunomodulation may be partly driven by Treg induction and/or expansion. However, these reports have not assessed Treg yield in terms of absolute counts, nor characterized the resulting Treg-like cells in detail. In the present study, Dr. Azevedo's team sought to determine whether MSC are able to induce and/or expand Treg in vitro, as well as the mechanisms of Treg enrichment by MSC.
To conduct the study, they collected human peripheral blood mononuclear cells - including T-cells - from healthy donors and co-cultured them with allogeneic bone marrow-derived MSC. Fourteen days later, the results showed an increase in the count and frequency of Treg cells -- four- and six-fold, respectively.
The MSC-induced Treg-like cells resemble Treg functionally, and importantly, their DNA methylation profile closely resembles that of natural Treg, indicating that this population is stable. DNA methylation is an important component in numerous cellular processes, including embryonic development. Errors in the methylation have been linked to several human diseases.
"Our data sheds new light into the origin, functional potential and stability of MSC-induced Treg-like cells, which are key features for their potential applicability in the clinical setting." Dr. Azevedo concluded. "The co-administration of MSC and Treg might have the potential to constitute a more effective cellular therapy approach by harnessing the suppressive capacity of both these immunomodulatory populations."
"This is an exciting advance", said Dr. Jan Nolta, Editor-in-Chief of STEM CELLS. "Dr. Azevedo and her team have defined important MSC-based mechanisms to induce and enrich Treg cells, which could have important future implications for the treatment of chronic diseases."
The full article, "Mesenchymal stromal cells induce regulatory T cells via epigenetic conversion of human conventional CD4 T cells in vitro," can be accessed at https://stemcellsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/stem.3185.
About the Journal: STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. The journal covers all aspects of stem cells: embryonic stem cells/induced pluripotent stem cells; tissue-specific stem cells; cancer stem cells; the stem cell niche; stem cell epigenetics, genomics and proteomics; and translational and clinical research. STEM CELLS is co-published by AlphaMed Press and Wiley.
About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes three internationally renowned peer-reviewed journals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines. STEM CELLS® is the world's first journal devoted to this fast paced field of research. THE ONCOLOGIST® is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. STEM CELLS TRANSLATIONAL MEDICINE® is dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.
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