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Bone Marrow Time Travel
Exploring the potential and preparing of the clinical practice
for bone marrow transplantation for rejuvenation.
for bone marrow transplantation for rejuvenation.
Current scientific research points to the potential of injecting own cryopreserved Bone Marrow (BM) and Hematopoietic Stem Cells (HSC) as a factor in increasing health and longevity.
1) Availability of proven methods of non-traumatic sampling of HSC and bone marrow (Gratwohl et al., 2013)
2 ) Proven possibility of long-term cryostorage of HSCs without damage and maintaining their functional status (Ragg, 2002)
3) The proven ability of HSC after returning to the bloodstream to independently migrate to the bone marrow and organize hematopoietic niches in it.
4) The presence of direct data on the increase in lifespan and healthspan of old mice when they are transplanted with the bone marrow of young mice (Das et al., 2019; Kovina et al., 2012, 2019; Rozman, 2019)
5) Population-based data on increased life expectancy in people undergoing bone marrow transplantation and HSCs, depending on the youth of the cell donor (a decrease in the age of the donor by 5 years is associated with an increase in the life expectancy of the recipient by 1 year) (Kollman et al., 2016)
Bone Marrow
The central organ of the immune and hematopoietic system responsible for the production of all immune cells and all blood cells (including red blood cells and platelets). In total, the bone marrow produces about 92% of the body's cells.
At the same time, the synthesis of all these cells provides one type of stem cell called hematopoietic (HSC). The abilities of HSCs are very wide, they can not only produce lymphoid and myeloid cells, but also provide themselves with everything necessary for organizing hematopoiesis niches. They also know how to migrate, so when transplanting bone marrow and HSC, it is enough to inject into a vein, and the cells themselves will find their way to the bone marrow and organize hematopoiesis there.
Aging
The bone marrow maintains the state of the whole organism, but with age, the destructive processes caused by aging begin in it. The number and activity of HSCs decrease, and only individual HSC clones remain, which perform their functions poorly and are prone to cancerous degeneration. It is believed that the main reason for the depletion of the HSC pool is mutagenesis caused by the acute signals forcing cells to divide and physiological stress. HSC clones that have accumulated mutations in the genes that control the control of DNA stability begin to dominate, leading to clonal hematopoiesis, a condition observed in 20% of older people over 80 years of age.
Another aging derived deregulative factor for stem cells is the extracellular matrix structure disruption. It becomes rigid due to collagen damage and stem cells cannot form niches in it correctly.
Another aging derived deregulative factor for stem cells is the extracellular matrix structure disruption. It becomes rigid due to collagen damage and stem cells cannot form niches in it correctly.
Rejuvination
The simplest approach that could become a tool for bone marrow rejuvenation would be autologous heterochronous transplantation. When a small part of the bone marrow would be taken from a person at a young age (up to 50 years) and stored under cryogenic conditions, not subject to stress and mutagenesis. At the same time, at the age of more than 65 years, it would be possible to return cryopreserved HSCs to the body to restore hematopoietic function.
At the same time, the introduction of such an approach requires additional studies on model animals to clarify all the unclear aspects of this therapy, in particular, the study of the necessary and sufficient amount of bone marrow for transplantation, the search for approaches to prepare the extracellular matrix for niche formation, and the study of the fundamental causes of mutagenesis as a factor in the depletion of the HSC pool and bone marrow aging.
At the same time, the introduction of such an approach requires additional studies on model animals to clarify all the unclear aspects of this therapy, in particular, the study of the necessary and sufficient amount of bone marrow for transplantation, the search for approaches to prepare the extracellular matrix for niche formation, and the study of the fundamental causes of mutagenesis as a factor in the depletion of the HSC pool and bone marrow aging.
Project global tasks
- The study of substituted hematopoiesis in old animalsAfter transplantation of bone marrow cells and HSC in young animals (estimation of the proportion of newly activated hematopoiesis depending on the number of transplanted cells) in the absence of prior chemotherapeutic treatment. Chemotherapy in modern medical practice precedes HSC transplantation even in conditions of autologous transplantation, but is not applicable for aging therapy due to a large number of side effects.01
- Identification of an effective dose of bone marrow cells and HSCsIncluding CD 34+ cells, sufficient to compensate for bone marrow dysfunction caused by aging.02
- The study of changes in the lifespan of miceWith heterochronous autologous HSC transplantation. That is, when using the same mouse as a donor and recipient after a period of time, instead of a pair of “young and old mice”.03
- Testing the theory of increasing the efficiency of HSCTransplantation and increasing the life expectancy of the recipient with preliminary rejuvenation of stem cell niches with deglycating agents.04
- Testing the theory of the possibility of blocking mutagenesis pathways in HSCsBy influencing molecular and physiological pathways that block organismal stress.05
Current research
- TransplantationStudy of the effectiveness of bone marrow transplantation in linear mice with elucidation of the effect of the concentration of injected cells on the percentage of substituted hematopoiesis
- ChemotherapyComparison of the efficiency of bone marrow transplantation under conditions of prior exposure to chemotherapy, antiglycating agents acting on intercellular matrix or direct transplantation without additional effects in mice of different ages.
- CharacteristicsStudy of the optimal characteristics of intravital HSC sampling in house mice
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