2017
DOI: 10.1126/scitranslmed.aan1145
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A distinct hematopoietic stem cell population for rapid multilineage engraftment in nonhuman primates

Abstract: Hematopoietic reconstitution after bone marrow transplantation is thought to be driven by committed multipotent progenitor cells followed by long-term engrafting hematopoietic stem cells (HSCs). We observed a population of early-engrafting cells displaying HSC-like behavior, which persisted long-term in vivo in an autologous myeloablative transplant model in nonhuman primates. To identify this population, we characterized the phenotype and function of defined nonhuman primate hematopoietic stem and progenitor … Show more

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Cited by 92 publications
(131 citation statements)
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“…Despite an inconsistent correlation between phenotype and function in studies evaluating the ex vivo expansion of human HSCs, 28 several studies have shown a strong association between the CD34+ CD45RA-CD90+ phenotype, and specifically CD90 (Thy1) expression, and the long-term repopulating capacity in vivo. 36,37 In the present study, VPA treatment led to a robust generation of a CD34+CD45RA-CD90+ cell population that correlated with HSC activity in functional studies and long-term repopulating capacity in vivo. In contrast, the lack of generation of phenotypically defined HSC subpopulations observed with cytokines alone control cultures correlated with poor engraftment outcomes under these culture conditions.…”
Section: Effect Of Vpa On Hscs From Adult Sources Is Comparable To supporting
confidence: 59%
“…Despite an inconsistent correlation between phenotype and function in studies evaluating the ex vivo expansion of human HSCs, 28 several studies have shown a strong association between the CD34+ CD45RA-CD90+ phenotype, and specifically CD90 (Thy1) expression, and the long-term repopulating capacity in vivo. 36,37 In the present study, VPA treatment led to a robust generation of a CD34+CD45RA-CD90+ cell population that correlated with HSC activity in functional studies and long-term repopulating capacity in vivo. In contrast, the lack of generation of phenotypically defined HSC subpopulations observed with cytokines alone control cultures correlated with poor engraftment outcomes under these culture conditions.…”
Section: Effect Of Vpa On Hscs From Adult Sources Is Comparable To supporting
confidence: 59%
“…[57] and Gao et al [58]. analyses of HSCs [61,62]. These data suggest that the TF profile of 3GF cells more closely resembles native HSCs than GGF cells.…”
Section: Expression Profiling Of 3gf Cells As They Undergo Reprogrammingmentioning
confidence: 85%
“…Notably, this analysis demonstrates clear upregulation of MAZ, RCOR1, and ZKSCAN1 in each 3GF population. analyses of HSCs [61,62]. RCOR1, another TF enriched in HSCs, is suggested to play an important role in HSC specification from the AGM and was also found to be upregulated in 3GF cells [60].…”
Section: Expression Profiling Of 3gf Cells As They Undergo Reprogrammingmentioning
confidence: 99%
“…One could envisage administering unmodified short-term progenitors which, having been spared ex vivo culture and transduction, should ensure faster reconstitution, admixed with transduced HSC, which would progressively replace the graft with gene-modified progeny (Zonari et al, 2017). Whereas HSC GT has been performed until now with cells purified according to surface expression of the CD34 marker, we can envisage exploring new protocols that further enrich for the repopulating HSPC fraction by adding other markers to the selection profile, provided that clinically compliant technologies for multi-parametric cell sorting coupled with advanced microfluidics become available (Notta et al, 2011;Fares et al, 2017;Radtke et al, 2017). Whereas HSC GT has been performed until now with cells purified according to surface expression of the CD34 marker, we can envisage exploring new protocols that further enrich for the repopulating HSPC fraction by adding other markers to the selection profile, provided that clinically compliant technologies for multi-parametric cell sorting coupled with advanced microfluidics become available (Notta et al, 2011;Fares et al, 2017;Radtke et al, 2017).…”
Section: Haceinmentioning
confidence: 99%
“…On the other hand, were only short-term progenitors transduced and administered, one might obtain a time-limited graft of transduced cell possibly restricted to selected lineages, best fitting genetic engineering applications fighting cancer and infection. Whereas HSC GT has been performed until now with cells purified according to surface expression of the CD34 marker, we can envisage exploring new protocols that further enrich for the repopulating HSPC fraction by adding other markers to the selection profile, provided that clinically compliant technologies for multi-parametric cell sorting coupled with advanced microfluidics become available (Notta et al, 2011;Fares et al, 2017;Radtke et al, 2017). HSC-enriched cell products would allow saving on culture volume and vector need, enabling more cost-effective industrialization of automated cell processing.…”
Section: Haceinmentioning
confidence: 99%