Ex vivo expansion of human hematopoietic stem and progenitor cells

Despite progress in our understanding of the growth factors that support the progressive maturation of the various cell lineages of the hematopoietic system, less is known about factors that govern the self-renewal of hematopoietic stem and progenitor cells (HSPCs), and our ability to expand human H...

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Published inBlood Vol. 117; no. 23; pp. 6083 - 6090
Main Authors Dahlberg, Ann, Delaney, Colleen, Bernstein, Irwin D.
Format Journal Article
LanguageEnglish
Published Washington, DC Elsevier Inc 09.06.2011
Americain Society of Hematology
American Society of Hematology
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Abstract Despite progress in our understanding of the growth factors that support the progressive maturation of the various cell lineages of the hematopoietic system, less is known about factors that govern the self-renewal of hematopoietic stem and progenitor cells (HSPCs), and our ability to expand human HSPC numbers ex vivo remains limited. Interest in stem cell expansion has been heightened by the increasing importance of HSCs in the treatment of both malignant and nonmalignant diseases, as well as their use in gene therapy. To date, most attempts to ex vivo expand HSPCs have used hematopoietic growth factors but have not achieved clinically relevant effects. More recent approaches, including our studies in which activation of the Notch signaling pathway has enabled a clinically relevant ex vivo expansion of HSPCs, have led to renewed interest in this arena. Here we briefly review early attempts at ex vivo expansion by cytokine stimulation followed by an examination of our studies investigating the role of Notch signaling in HSPC self-renewal. We will also review other recently developed approaches for ex vivo expansion, primarily focused on the more extensively studied cord blood–derived stem cell. Finally, we discuss some of the challenges still facing this field.
AbstractList Despite progress in our understanding of the growth factors that support the progressive maturation of the various cell lineages of the hematopoietic system, less is known about factors that govern the self-renewal of hematopoietic stem and progenitor cells (HSPCs), and our ability to expand human HSPC numbers ex vivo remains limited. Interest in stem cell expansion has been heightened by the increasing importance of HSCs in the treatment of both malignant and nonmalignant diseases, as well as their use in gene therapy. To date, most attempts to ex vivo expand HSPCs have used hematopoietic growth factors but have not achieved clinically relevant effects. More recent approaches, including our studies in which activation of the Notch signaling pathway has enabled a clinically relevant ex vivo expansion of HSPCs, have led to renewed interest in this arena. Here we briefly review early attempts at ex vivo expansion by cytokine stimulation followed by an examination of our studies investigating the role of Notch signaling in HSPC self-renewal. We will also review other recently developed approaches for ex vivo expansion, primarily focused on the more extensively studied cord blood-derived stem cell. Finally, we discuss some of the challenges still facing this field.
Author Bernstein, Irwin D.
Dahlberg, Ann
Delaney, Colleen
Author_xml – sequence: 1
  givenname: Ann
  surname: Dahlberg
  fullname: Dahlberg, Ann
  organization: Pediatric Oncology, Clinical Division, Fred Hutchinson Cancer Research Center, Seattle, WA
– sequence: 2
  givenname: Colleen
  surname: Delaney
  fullname: Delaney, Colleen
  organization: Pediatric Oncology, Clinical Division, Fred Hutchinson Cancer Research Center, Seattle, WA
– sequence: 3
  givenname: Irwin D.
  surname: Bernstein
  fullname: Bernstein, Irwin D.
  email: ibernste@fhcrc.org
  organization: Pediatric Oncology, Clinical Division, Fred Hutchinson Cancer Research Center, Seattle, WA
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Issue 23
Keywords Human
Hematopoietic cell
Ex vivo
Hematology
Expansion
Stem cell
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PublicationTitle Blood
PublicationTitleAlternate Blood
PublicationYear 2011
Publisher Elsevier Inc
Americain Society of Hematology
American Society of Hematology
Publisher_xml – name: Elsevier Inc
– name: Americain Society of Hematology
– name: American Society of Hematology
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Snippet Despite progress in our understanding of the growth factors that support the progressive maturation of the various cell lineages of the hematopoietic system,...
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SubjectTerms Biological and medical sciences
Cell Culture Techniques - methods
Cytokines - pharmacology
Fetal Blood - cytology
Fetal Blood - metabolism
Hematologic and hematopoietic diseases
Hematopoiesis and Stem Cells
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - metabolism
Humans
Medical sciences
Receptors, Notch - metabolism
Review
Signal Transduction - drug effects
Title Ex vivo expansion of human hematopoietic stem and progenitor cells
URI https://dx.doi.org/10.1182/blood-2011-01-283606
https://www.ncbi.nlm.nih.gov/pubmed/21436068
https://search.proquest.com/docview/871386841
https://pubmed.ncbi.nlm.nih.gov/PMC3122936
Volume 117
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