Functional Isolation and Characterization of Human Hematopoietic Stem Cells

Berardi, Anna C.; Wang, Anlai; Levine, James D.; Lopez, Peter; Scadden, David T.

doi:10.1126/science.7528940

Cited by 378 publications

(220 citation statements)

References 44 publications

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“…CD34 is a transmembrane phosphoglycoprotein with L‐selectin (CD62L) as its most commonly described ligand 49. Ubiquitous CD34 expression is related to hematopoietic cells, and it serves as a marker to enrich hematopoietic stem cells for bone marrow transplants 50. CD34 + non‐hematopoietic lineage cells also represent a distinct subset of cells with enhanced progenitor activity, such as muscle satellite cells, interstitial cells, epithelial progenitors and CSKs 51.…”

Section: Discussionmentioning

confidence: 99%

Postnatal periodontal ligament as a novel adult stem cell source for regenerative corneal cell therapy

Yam

Teo

Setiawan

et al. 2018

J Cellular Molecular Medi

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Corneal opacities are a leading cause of global blindness. They are conventionally treated by the transplantation of donor corneal tissue, which is, restricted by a worldwide donor material shortage and allograft rejection. Autologous adult stem cells with a potential to differentiate into corneal stromal keratocytes (CSKs) could offer a suitable choice of cells for regenerative cell therapy. Postnatal periodontal ligament (PDL) contains a population of adult stem cells, which has a similar embryological origin as CSK, that is cranial neural crest. We harvested PDL cells from young adult teeth extracted because of non‐functional or orthodontic reason and differentiated them towards CSK phenotype using a two‐step protocol with spheroid formation followed by growth factor and cytokine induction in a stromal environment (human amnion stroma and porcine corneal stroma). Our results showed that the PDL‐differentiated CSK‐like cells expressed CSK markers (CD34, ALDH3A1, keratocan, lumican, CHST6, B3GNT7 and Col8A2) and had minimal expression of genes related to fibrosis and other lineages (vasculogenesis, adipogenesis, myogenesis, epitheliogenesis, neurogenesis and hematogenesis). Introduction of PDL spheroids into the stroma of porcine corneas resulted in extensive migration of cells inside the host stroma after 14‐day organ culture. Their quiescent nature and uniform cell distribution resembled to that of mature CSKs inside the native stroma. Our results demonstrated the potential translation of PDL cells for regenerative corneal cell therapy for corneal opacities.

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Section: Discussionmentioning

confidence: 99%

Postnatal periodontal ligament as a novel adult stem cell source for regenerative corneal cell therapy

Yam

Teo

Setiawan

et al. 2018

J Cellular Molecular Medi

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“…44 In contrast, the most primitive hemopoietic cells have a low expression or even lack GM-CSFR expression. 34,[44][45][46] AML cells express equal numbers of GM-CSFR as do the CFU-GM. 43 Therefore, the difference in sensitivity between the AML cells and the committed CFU-GM is not explained by differences in receptor number.…”

Section: Discussionmentioning

confidence: 99%

In vivo targeting of leukemic cells using diphtheria toxin fused to murine GM-CSF

et al. 1998

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We have previously demonstrated that diphtheria toxin (DT) fused to human GM-CSF effectively eliminates human longterm leukemia initiating cells in SCID mice. However, because huGM-CSF does not react with the murine GM-CSF receptor possible side-effects to nonleukemic tissues could not be analyzed in the AML/SCID model. To overcome this problem, we used murine GM-CSF fused to DT and studied the therapeutic index in the rat leukemia model BNML/LT12. In DT-mGM-CSF dose escalation experiments, severe dose-dependent toxicity to organs such as liver, kidney and lung was observed. Therefore, the antileukemic effects were evaluated with the lower doses. Daily intraperitoneal bolus injections of 75 g/kg/day for 7 days induced a 3 log leukemic cell kill. The dose of 75 g/kg/day had no effect on the hemopoietic progenitor cell subsets. These in vivo studies show that the DT-GM-CSF fusion protein can be used for specifically targeting leukemic cells and thus has potential as a therapeutic agent in the treatment of AML.

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“…The human bone grafts removed eight weeks after cell injection were analyzed for donor cell content by flow cytometry [18,20]. …”

Section: Cells Refractory To Cd43-mediated Apoptosis Engraft In Humanmentioning

confidence: 99%

Resistance of human hematopoietic stem cells to a monoclonal antibody recognizing CD43

Bažil¹,

Brandt²,

Hoffman³

1997

Stem Cells

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Hematopoietic progenitor cells (HPC) interact with bone marrow stroma by adhesion molecules which are thought to be critically important to the regulation of hematopoiesis. The specific roles of individual adhesion molecules involved in these interactions remain poorly understood. A monoclonal antibody (mAb) recognizing CD43, an adhesion molecule highly expressed by HPC, induces apoptosis in CD34hi Lin− marrow cells. This process operates at a single‐cell level, and the initiation of apoptosis requires crosslinking of surface CD43 and the presence of cytokines. In contrast to HPC, more differentiated hematopoietic cells do not undergo apoptosis in response to the CD43‐mediated stimulation. Not all progenitor cells undergo apoptosis upon stimulation of CD43. Dividing progenitor cells are most affected, whereas more primitive, quiescent cells survive anti‐CD43 mAb treatment. These surviving cells: A) are enriched for cobblestone area‐forming cells; B) repopulate fragments of human fetal bone implanted into CX.B‐17 severe combined immunodeficiency (SCID/hu) mice; C) have a potential to differentiate in vivo to myeloid and lymphoid cells, and D) have a high proliferative potential in long‐term stromal cell‐free liquid culture. These data indicate that cells with hematopoietic stem cell characteristics are relatively resistant to CD43‐mediated apoptosis compared to HPC and that CD43 may function as a negative regulator of early events occurring during hematopoiesis. Stem Cells 1997; 15(suppl 1): 13–19

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Functional Isolation and Characterization of Human Hematopoietic Stem Cells

Cited by 378 publications

References 44 publications

Postnatal periodontal ligament as a novel adult stem cell source for regenerative corneal cell therapy

Postnatal periodontal ligament as a novel adult stem cell source for regenerative corneal cell therapy

In vivo targeting of leukemic cells using diphtheria toxin fused to murine GM-CSF

Resistance of human hematopoietic stem cells to a monoclonal antibody recognizing CD43

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