The potential of human peripheral blood derived CD34+ cells for ex vivo red blood cell production

Metabolic profiling of hematopoietic stem and progenitor cells during proliferation and differentiation into red blood cells

“…Growth rate decreased significantly in late proliferation phase and was negligible during differentiation and maturation phases. These results are in agreement with previous studies [1].…”

“…Several groups have attempted to generate significant numbers of erythroid cells from the HSPCs in mobilized peripheral blood, bone marrow (BM), and umbilical cord blood (UCB), as well as from human embryonic stem cells and induced pluripotent stem cells [1][2][3][4][5]. The most successful of these to date showed enucleation levels of 100 percent with up to 1.95 Â 10 6 -fold expansion by using a three-phase culture system that included coculture with a stromal cell line [6].…”

Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin

“…For comparison, the mean expansion of adult CD34 + /CD45 + HSC (n=8), cultured under the same conditions, is 89,000-fold, with homogeneous differentiation into enucleated RBC (85.2%±4.8%) that express mainly adult hemoglobin (unpublished data). When using CD34 + cells from CB, established protocols with expansion rates of up to 1.96x10 6 fold will theoretically allow for the generation of more than 3x10 12 RBC from one CB unit. 1 However, the erythroid differentiation potential of the human iPSC described here is similar to that in recent studies using fibroblast and mesenchymal stromal cell-derived iPSC in embryoid body 18,21 or stromal layer-based culture systems.…”

“…Using human hematopoietic stem cells (HSC) from cord blood (CB) or bone marrow as the primary source, expansion rates higher than 10 5 -fold, [1][2][3][4][5][6] accompanied by fully terminal maturation into enucleated reticulocytes, [1][2][3][4] have been achieved. Recently, the first proof-of-principle experiment was performed by transfusing a small sample of manufactured RBC into a human recipient.…”

Potenzial hämatopoetischer Stammzellen als Ausgangsmaterial für Arzneimittel für neuartige Therapien

“…Die Enukleation von Erythrozyten wird -auch bei Kokultur mit Makrophagen, die in vivo die erythropoetische Nische bilden -in der Regel nicht vollständig erreicht. Dennoch ist es gelungen, in vitro einige µl hämoglobin-haltige, zum Sauerstofftransport befähig-te Zellen zu produzieren, die Erythrozyten entsprachen [40,41]. Ebenso gelang es, CD34 + -Zellen zu (Pro-)Megakaryozyten auszureifen beziehungsweise Megakaryozyten in vitro dazu zu bringen, Abschnürungen zu generieren.…”