Expansion of hematopoietic stem cells for transplantation: current perspectives

Schuster, Jessica A.; Stupnikov, Maria R; Ma, Gina; Liao, Wenbin; Lai, Raymond; Ma, Yupo; Aguila, Jerell R

doi:10.1186/2162-3619-1-12

Cited by 30 publications

(26 citation statements)

References 31 publications

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“…Besides the generation of distinct hematopoietic lineages, the generation of HSCs from hiPSCs is a central purpose of biomedical research and transfusion medicine in particular [24,25]. Although significant efforts were done, true HSCs with long-term engraftment potential cannot be expanded indefinitely in vitro until now [26,27]. In contrast, undifferentiated hiPSCs can theoretically be expanded indefinitely in vitro while maintaining their pluripotency for all three germ layers; they can be stored, thawed, and differentiated into the desired tissue afterwards as well as bioengineered orgene-modified on demand.…”

Section: Discussionmentioning

confidence: 99%

Emergence of CD43-Expressing Hematopoietic Progenitors from Human Induced Pluripotent Stem Cells

Kessel¹,

Bluemke²,

Schöler³

et al. 2017

Transfus Med Hemother

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Background: The ex vivo generation of human hematopoietic stem cells (HSCs) with long-term repopulating capacity and multi-lineage differentiation potential represents the holy grail of hematopoiesis research. In principle, human induced pluripotent stem cells (hiPSCs) provide the tool for both studying molecular mechanisms of hematopoietic development and the ex vivo production of ‘true' HSCs for transplantation purposes and lineage-specific cells, e.g. red blood cells, for transfusion purposes. CD43-expressing cells have been reported as the first hematopoietic cells during development, but whether or not these possess multilineage differentiation and long-term engraftment potential is incompletely understood. Methods: We performed ex vivo generation of hematopoietic cells from hiPSCs using an embryoid body(EB)-based, xeno-product-free differentiation protocol. We investigated the multilineage differentiation potential of different FACS-sorted CD43-expressing cell subsets by colony-forming assays in semisolid media. Further, erythroid differentiation was investigated in more detail using established protocols. Results: By using CD43, we were able to measure hematopoietic induction efficiency during hiPSC-derived EB differentiation. Further, we determined CD43+ cells as the cell population of origin for in vitro erythropoiesis. Furthermore, colony formation demonstrates that the multipotent hematopoietic stem and progenitor cell fraction is particulary enriched in the CD43^hi CD45+ population.

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Section: Discussionmentioning

confidence: 99%

Emergence of CD43-Expressing Hematopoietic Progenitors from Human Induced Pluripotent Stem Cells

Kessel¹,

Bluemke²,

Schöler³

et al. 2017

Transfus Med Hemother

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“…What knowledge can we obtain from developmental biology, and in particular, from analyzing hematopoietic development in the embryo which is of clinical relevance? One of the greatest challenges of modern hematology is the ex vivo expansion of human cord blood HSC as this has the potential to secure the safety of donors and solve the donor shortage in HSC transplantation for hematopoietic diseases [5152]. Various methods have been reported to improve the ex vivo expansion of human cord blood derived HSCs.…”

Section: Introductionmentioning

confidence: 99%

Regulation of the embryonic erythropoietic niche: a future perspective

2017

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The production of red blood cells, termed erythropoiesis, occurs in two waves in the developing mouse embryo: first primitive erythropoiesis followed by definitive erythropoiesis. In the mouse embryo, both primitive and definitive erythropoiesis originates in the extra-embryonic yolk sac. The definitive wave then migrates to the fetal liver, fetal spleen and fetal bone marrow as these organs form. The fetal liver serves as the major organ for hematopoietic cell expansion and erythroid maturation after mid-gestation. The erythropoietic niche, which expresses critical cytokines such as stem cell factor (SCF), thrombopoietin (TPO) and the insulin-like growth factors IGF1 and IGF2, supports hematopoietic expansion in the fetal liver. Previously, our group demonstrated that DLK1+ hepatoblasts support fetal liver hematopoiesis through erythropoietin and SCF release as well as extracellular matrix deposition. Loss of DLK1+ hepatoblasts in Map2k4−/− mouse embryos resulted in decreased numbers of hematopoietic cells in fetal liver. Genes encoding proteinases and peptidases were found to be highly expressed in DLK1+ hepatoblasts. Capitalizing on this knowledge, and working on the assumption that these proteinases and peptidases are generating small, potentially biologically active peptides, we assessed a range of peptides for their ability to support erythropoiesis in vitro. We identified KS-13 (PCT/JP2010/067011) as an erythropoietic peptide-a peptide which enhances the production of red blood cells from progenitor cells. Here, we discuss the elements regulating embryonic erythropoiesis with special attention to niche cells, and demonstrate how this knowledge can be applied in the identification of niche-derived peptides with potential therapeutic capability.

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“…Recently, SALL4 has been shown to play an important role in maintaining ES cell (ESC) pluripotency and self-renewal properties. SALL4 is involved in the self-renewal of leukemic initiation and HSPC [14]. Moreover, recent data have shown that SALL4 plays an essential role in myeloid leukemogenesis.…”

Section: Introductionmentioning

confidence: 99%

The differential expression pattern of the BMI-1, SALL4 and ABCA3 genes in myeloid leukemia

Shen

Liu

et al. 2012

Cancer Cell Int

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Background and methodsIn order to characterize the expression pattern of SALL4, BMI-1 and ABCA3 genes in patients with myeloid leukemia and those who achieved complete remission (CR) after chemotherapy. Real-time PCR was used to determine the expression level of these genes in peripheral blood mononuclear cells from 24 patients with AML, eight patients with AML-CR, 13 patients with CML in the chronic phase (CML-CP), 12 patients with CML in blast crisis (CML-BC), 13 patients with CML-CR and 11 healthy individuals (HI).ResultsOverexpression of the BMI-1 gene was found in the AML, CML-CP and CML-BC groups as compared with HI group, while the BMI-1 expression level was lower in patients who achieved CR. In contrast, significantly increased SALL4 expression was only found in AML group, additionally, SALL4 expression was lower in the CML-CP and CML-CR groups compared with the HI group, while the SALL4 expression level in the CML-BC group was higher and significantly greater than that in the CML-CP and CML-CR groups. Moreover, a positive correlation between the expression of SALL4 and BMI-1 genes was found in samples from most groups. There was no significant difference of ABCA3 expression level in AML and CML-BC group in comparison with HI group. Interestingly, the ABCA3 expression level was significantly decreased in the CML-CP, AML-CR and CML-CR in comparison with the HI group. Moreover, the ABCA3 expression level in all of the CR groups was lower than that in their corresponding groups.ConclusionsThese results describe the altered SALL4, ABCA3 and BMI-1 expression pattern in different phases of myeloid leukemia, which may relate to the development and progression to different diseases. SALL4 expression was strongly correlated with BMI-1 in most of the myeloid leukemia patient groups, providing a potential link between SALL4 and BMI-1 in leukemogenesis.

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Expansion of hematopoietic stem cells for transplantation: current perspectives

Cited by 30 publications

References 31 publications

Emergence of CD43-Expressing Hematopoietic Progenitors from Human Induced Pluripotent Stem Cells

Emergence of CD43-Expressing Hematopoietic Progenitors from Human Induced Pluripotent Stem Cells

Regulation of the embryonic erythropoietic niche: a future perspective

The differential expression pattern of the BMI-1, SALL4 and ABCA3 genes in myeloid leukemia

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