In cases such as bone marrow transplantation, which involves the transplantation of hematopoietic stem cells, namely stem cells that give rise to other types of blood cells, a younger donor age results in a better outcome. A group of Indian scientists have now developed a mechanism that can rejuvenate stem cells from older donors, making them useful for transplantation.
The mechanism developed by researchers at the National Centre for Cell Science (NCCS), Pune, involves rejuvenating aged hematopoietic stem cells in a short-term culture using micro-vesicles secreted by young stromal cells.
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This approach, they hope, will expand donor cohort.
The finding has relevance in clinical bone-marrow transplantation, wherein aged donors are usually not preferred as their stem cells could have compromised engraftment ability due to ageing. With the new mechanism, it might be possible to rejuvenate aged stem cells and thereby expand the donor pool.
“Stromal cells are support cells present in the micro-environment of stem cells. We have shown that these cells display activated AkT signalling as they age. This leads to a loss of autophagy-inducing mRNAs in their micro-vesicles. If this signalling is blocked by using chemical inhibitors in aged stromal cells in culture, they become ‘young-like’ and secrete good quality micro-vesicles containing autophagy-inducing mRNA that can rejuvenate aged stem cells,” explains Dr. Vaijayanti P. Kale, who led the research team. The findings have been published in the scientific journal,
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Study using mice
For the study, researchers used 6-8 week (young) and 18-24 month (aged) old mice because age-associated changes in human hematopoietic stem cells are similar to those observed in mice, suggesting that hematopoietic ageing is an evolutionarily-conserved process. Their bone marrow derived lineage-negative cells were treated with extra-cellular vesicles, micro-vesicles or exosomes isolated from a conditioned medium of mesenchymal stromal cells for 36 hours. The output cells were subjected to phenotypic, functional and molecular characterisations. They observed that young mesenchymal stromal cells rejuvenate aged hematopoietic stem cells.
“Our data indicates that such rejuvenation may also be possible for other tissue-specific stem cells. We propose to extend our research towards stem cells from other tissues,” says Dr. Kale. She also adds that this research has the potential to improve the outcome of regenerative medicine therapies using this approach. — India Science Wire