scholarly journals Lost in Transplantation? Unexpected shift from multipotent to late lymphomyeloid hematopoietic stem and progenitor cells in patients 1 year after hematopoietic stem cell transplantation

2016 ◽  
Vol 51 (8) ◽  
pp. 1073-1075 ◽  
Author(s):  
A Görgens ◽  
F Murke ◽  
L Kordelas ◽  
B Giebel
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Progenitor Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

scholarly journals Transient apoptosis inhibition in donor stem cells improves hematopoietic stem cell transplantation

2017 ◽  
Vol 214 (10) ◽  
pp. 2967-2983 ◽  
Author(s):  
Matthias Kollek ◽  
Gesina Voigt ◽  
Christian Molnar ◽  
Fabronia Murad ◽  
Daniela Bertele ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Progenitor Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Apoptosis Inhibition ◽  
Donor Cells ◽  
Stem And Progenitor Cells

During hematopoietic stem cell transplantation, a substantial number of donor cells are lost because of apoptotic cell death. Transplantation-associated apoptosis is mediated mainly by the proapoptotic BCL-2 family proteins BIM and BMF, and their proapoptotic function is conserved between mouse and human stem and progenitor cells. Permanent inhibition of apoptosis in donor cells caused by the loss of these BH3-only proteins improves transplantation outcome, but recipients might be exposed to increased risk of lymphomagenesis or autoimmunity. Here, we address whether transient inhibition of apoptosis can serve as a safe but efficient alternative to improve the outcome of stem cell transplantation. We show that transient apoptosis inhibition by short-term overexpression of prosurvival BCL-XL, known to block BIM and BMF, is not only sufficient to increase the viability of hematopoietic stem and progenitor cells during engraftment but also improves transplantation outcome without signs of adverse pathologies. Hence, this strategy represents a promising and novel therapeutic approach, particularly under conditions of limited donor stem cell availability.

scholarly journals GPRASP proteins are critical negative regulators of hematopoietic stem cell transplantation

Blood ◽  
2020 ◽  
Author(s):  
Antonio Morales-Hernandez ◽  
Chaïma Benaksas ◽  
Ashley Chabot ◽  
Claire Caprio ◽  
Maheen Ferdous ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Molecular Mechanisms ◽  
Negative Regulators ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Stem And Progenitor Cells

Hematopoietic stem cell transplantation (HSCT) is often exploited to treat hematologic disease. Donor HSCs must survive, proliferate and differentiate in the damaged environment of the reconstituting niche. Illuminating molecular mechanisms regulating the activity of transplanted HSCs will inform efforts to improve HSCT. Here, we report that GPRASP proteins function as negative regulators of HSCT. Silencing of Gprasp1 or Gprasp2 increased the survival, quiescence, migration, niche retention and hematopoietic repopulating activity of hematopoietic stem and progenitor cells (HSPCs) post-transplant. We further show that GPRASP1 and GPRASP2 promote the degradation of CXCR4, a master regulator of HSC function during transplantation. CXCR4 accumulates in Gprasp-deficient HSPCs, boosting their function post-transplant. Thus, GPRASPs negatively regulate CXCR4 stability in HSCs. Our work reveals GPRASP proteins as negative regulators of HSCT and CXCR4 activity. Disruption of GPRASP/CXCR4 interactions could be exploited in the future to enhance the efficiency of HSCT.

scholarly journals Hematopoietic stem cell transplantation alters susceptibility to pulmonary hypertension in Bmpr2-deficient mice

2018 ◽  
Vol 8 (4) ◽  
pp. 204589401880164 ◽  
Author(s):  
Alexi Crosby ◽  
Mark R. Toshner ◽  
Mark R. Southwood ◽  
Elaine Soon ◽  
Benjamin J. Dunmore ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Progenitor Cells ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Low Dose ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Hematopoietic Stem

Increasing evidence suggests that patients with pulmonary arterial hypertension (PAH) demonstrate abnormalities in the bone marrow (BM) and hematopoietic progenitor cells. In addition, PAH is associated with myeloproliferative diseases. We have previously demonstrated that low-dose lipopolysaccharide (LPS) is a potent stimulus for the development of PAH in the context of a genetic PAH mouse model of BMPR2 dysfunction. We hypothesized that the hematopoietic progenitor cells might be driving disease in this model. To test this hypothesis, we performed adoptive transfer of BM between wild-type (Ctrl) and heterozygous Bmpr2 null (Mut) mice. Sixteen weeks after BM reconstitution, mice were exposed to low-dose chronic LPS (0.5 mg/kg three times a week for six weeks). Mice underwent right heart catheterization and tissues were removed for histology. After chronic LPS dosing, Ctrl mice in receipt of Mut BM developed PAH, whereas Mut mice receiving Ctrl BM were protected from PAH. BM histology demonstrated an increase in megakaryocytes and there was an increase in circulating platelets in Ctrl mice receiving Mut BM. These findings demonstrate that the hematopoietic stem cell compartment is involved in the susceptibility to PAH in the Mut mouse. The results raise the possibility that hematopoietic stem cell transplantation might be a potential treatment strategy in genetic forms of PAH.

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