Protection of hematopoietic stem cells from stress-induced exhaustion and aging

Purpose of review Hematopoietic stem cells (HSCs) are defined by their ability to self-renew and differentiate to replenish all blood lineages throughout adult life. Under homeostasis, the majority of HSCs are quiescent, and few stem cells are cycling to sustain hematopoiesis. However, HSCs can be induced to proliferate and differentiate in response to stress signals produced during infection, inflammation, chemotherapy, radiation, bone marrow transplantation, and aging. Recent evidence suggests that acute and chronic stress impact the number and function of HSCs including their ability to repopulate and produce mature cells. This review will focus on how chronic stress affects HSC biology and methods to mitigate HSC loss during chronic hematopoietic stress. Recent findings Quiescent HSCs exit dormancy, divide, and differentiate to maintain steady-state hematopoiesis. Under conditions of acute stress including infection or blood loss some HSCs are pushed into division by cytokines and proinflammatory stimuli to differentiate and provide needed myeloid and erythroid cells to protect and reconstitute the host; after which, hematopoiesis returns to steady-state with minimal loss of HSC function. However, under conditions of chronic stress including serial bone marrow transplantation (BMT), chronic inflammation, and genotoxic stress (chemotherapy) and aging, HSCs are continuously induced to proliferate and undergo accelerated exhaustion. Recent evidence demonstrates that abl...
Source: Current Opinion in Hematology - Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research

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our M Abstract Microtransplantation (MT) is based on injection of HLA-mismatched G-CSF mobilized hematopoietic stem cells, in combination with chemotherapy but without use of conditioning regimen nor immunosuppressive drugs. As a result, a transient microchimerism is induced without engraftment. Its efficacy relies both on host immune system stimulation (recipient versus tumor) and on a graft versus tumor effect. Data are scarce and concern mostly Asian patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (HR-MDS). In comparison to conventional treatment without MT, higher complete rem...
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research
The role of bridging therapy with intensive chemotherapy and/or hypomethylating agents followed by hematopoietic stem cell transplantation (HSCT) has been suggested, but there is some controversy regarding the influence of treatment response on transplant outcomes1. Considering this context, here we have investigated the influence of treatment prior to HSCT in patients with MDS.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: Brief Article Source Type: research
In conclusion, taller body height at the entry to adulthood, supposed to be a marker of early-life environment, is associated with lower risk of dementia diagnosis later in life. The association persisted when adjusted for educational level and intelligence test scores in young adulthood, suggesting that height is not just acting as an indicator of cognitive reserve. A Comparison of Biological Age Measurement Approaches https://www.fightaging.org/archives/2020/02/a-comparison-of-biological-age-measurement-approaches/ Researchers here assess the performance of a range of approaches to measuring biological...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Stem cell populations become damaged and dysfunctional with age. Some of this is issues with the stem cells themselves, and some of this results from problem with the signaling environment and function of the stem cell niche. Which of these factors is more important likely varies by stem cell population. Among the best studied of stem cell types, the evidence suggests that muscle stem cells remain capable in old age, but become ever more quiescent, while hematopoietic stem cells become damaged and dysfunctional, unable to perform. Hematopoietic stem cells reside in the bone marrow and are responsible for generating blood a...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
This is the latest in a series of yearly posts in which I suggest areas of development for biotech startups I'd like to see actively developed as a part of the longevity industry in the near future. Today, this year, is a good time to be starting a company focused on the production of a novel therapeutic approach to intervening in the aging process. There is a great deal of funding for seed stage investment, and many compelling projects lacking champions, yet to be carried forward from academia into preclinical development. Numerous scientific and industry crossover conferences are now held every year, at which it is possi...
Source: Fight Aging! - Category: Research Authors: Tags: Investment Source Type: blogs
Most patients suffering from classical Hodgkin's lymphoma (cHL) can be treated successfully with standard chemo- and/or radiotherapy, with 70% of them being alive 10 years after diagnosis. The gold standard treatment for patients that fail first-line treatment is high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (autoHSCT).1-4 Patients who fail autoHSCT (or at least two prior lines of therapy) may be treated with brentuximab vedotin (Bv); however, in many patients the disease will progress, with a median overall survival (OS) of approximately 22 months.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Radiolabeled CD45 antibodies have demonstrated clinical promise as targeted conditioning agents prior to bone marrow transplant (BMT) as a better tolerated and potentially more effective alternative to chemotherapy and/or total body irradiation myeloablative conditioning regimens. CD45 is expressed on all immune cells, including hematopoietic stem cells and both precursor and mature lymphoid and myeloid cells, making it an ideal antigen for directing targeted radiation for conditioning. It is also highly expressed on most hematological cancers, offering the potential for a substantial anti-tumor effect.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 231 Source Type: research
Bone Marrow Transplantation, Published online: 20 January 2020; doi:10.1038/s41409-020-0789-5Intensive chemotherapy and up-front stem cell transplant for double hit lymphoma
Source: Bone Marrow Transplantation - Category: Hematology Authors: Source Type: research
Bone Marrow Transplantation, Published online: 25 November 2019; doi:10.1038/s41409-019-0756-1The timing of plerixafor addition to G-Csf and chemotherapy affects immunological recovery after autologous stem cell transplant in multiple myeloma
Source: Bone Marrow Transplantation - Category: Hematology Authors: Source Type: research
In conclusion, up-front UBMT was superior to up-front CBT in the low-risk group, but the strategies were comparable in the intermediate- and high-risk groups. PMID: 31701480 [PubMed - as supplied by publisher]
Source: International Journal of Hematology - Category: Hematology Authors: Tags: Int J Hematol Source Type: research
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