Scientists explore the rejuvenation potential of stem cell therapy

Scientists explore the rejuvenation potential of stem cell therapy The researchers have used a new strategy of bone marrow transplantation in mice, which does not involve radio- and/or chemotherapy. As a result, old mice that had received stem cells from younger inbred animals lived 30% longer.

Stem cells, although known to scientists for several decades, still hold many secrets about their functions and potential for medical applications. Researchers usually focus on 2 major properties of stem cells — self-renewal (ability to go through numerous cycles of cell growth and cell division, while maintaining the undifferentiated state) and potency (capacity to differentiate into other, specialised cell types). Stem cells are abundant in the bone marrow, and the existing therapy implies bone marrow transplantation to a patient — it is often recommended for those who suffer from leukaemia and lymphoma. The prospective to use stem cells for other purposes, such as antiaging therapy, pushes researchers to explore new strategies. Sechenov University scientists have performed experiments on mice that allowed old animals to live 30% longer, thanks to bone marrow transplantation. These results have been published in Frontiers in Genetics.

In this study, young mice were culled, and bone marrow was taken from them for transplantation into older animals by intravenous injection. What makes this work unusual is a large number of transplanted cells (100 million) that outmatches any previous reports, and the close genetic backgrounds of the animals. The mice were from the same herd, with a high degree of inbreeding — so the old animals would have been very unlikely to reject the transplants, as the tissue had originated from syngeneic donors.

It is the first time that bone marrow transplantation was performed in nonablated old mice — aged 15 months — when half the population had already died of old age. The study authors decided to avoid conventional approaches such as chemo- and/or radiotherapy, which are normally used to suppress the immune system. It is because they used safe adult stem cells that do not carry any teratogenic (oncogenic) risks, like embryonal or inducible stem cells. With the non-invasive treatment, the survival rate was boosted. The maximum lifespan of the mice that had received the transplants increased by almost 30%. It corresponds to a 3-fold increase in the living-after-treatment time, which in the human scale would mean an increase from 12+ to 39+ additional years of life if treated at the age of 75. The increase in the maximum lifespan is the most significant indicator of hitting the basic mechanisms of ageing, in particular the age-related loss of stem cells.

The researchers also investigated the fate of the transplants. To address this, the experiment included only mice of the B10-GFP line, which is heterozygous for the green fluorescent protein (GFP) transgene. The young mice used as donors were GFP-positive, and the old recipient animals were GFP-negative. As a result, after bone marrow transplantation, it was possible to detect fluorescence in the recipients’ tissues, since only donor cells could be fluorescent. The fluorescent signal, although reduced, was observed in the recipient animals’ bone marrow even 6 months after the transplantation. The degree of chimerism was 28%, indicating the number of bone marrow cells of donor origin at that point. Fluorescent cells were found in the spleen, kidneys, liver, and muscles. According to the authors, the extended lifespan could be attributed to cellular replacement, not just the paracrine effects.

Marina Kovina, of the Institute for Regenerative Medicine at Sechenov University, is the corresponding author of the paper. According to her, “transplantation was initiated at the age when half of the population had already died of old age. By this age, the stem cell count in the bone marrow falls by more than 10 times, and the replacement with the transplanted material can occur without the myeloablative conditioning of the recipients. At the age of 19.3 months, when the last mouse of the control (untreated) group died sedentary, almost immobile, and hunchback with poor hair, the transplanted mice were active, had an even spine, and nice shiny hair”.

The results led the authors to advocate for more rapid implementation of non-ablative stem cell transplantation into the clinic — not only for the treatment of pathologies but also for rejuvenation purposes. The efficiency of stem cell transplantation can be further increased by optimising the methods of selection, preparation, conditioning, and storage of stem cells. The authors are set to explore the rejuvenation potential of endometrial cells in their future work that will involve preclinical animal studies — to open new avenues for antiaging therapy.

This work was carried out by the Institute for Regenerative Medicine and the Department of Hospital Surgery (Sechenov University) in collaboration with the Institute of Cell Biophysics (Russian Academy of Sciences), the Institute of General Pathology and Pathophysiology (Russian Academy of Sciences), and the Department of Molecular Immunology at Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (Russian Academy of Sciences).

Read more: Kovina MV, Karnaukhov AV, Krasheninnikov ME, Kovin AL, Gazheev ST, Sergievich LA, Karnaukhova EV, Bogdanenko EV, Balyasin MV, Khodarovich YM, Dyuzheva TG, Lyundup AV. Extension of Maximal Lifespan and High Bone Marrow Chimerism After Nonmyeloablative Syngeneic Transplantation of Bone Marrow From Young to Old Mice. Front. Genet. (2019).

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