A robust potency assay highlights significant donor variation of human mesenchymal stem/progenitor cell immune modulatory capacity and extended radio-resistance

The inherent immunomodulatory capacity of mesenchymal stem/progenitor cells (MSPCs) encouraged initiation of multiple clinical trials. Release criteria for therapeutic MSPCs cover identity, purity and safety but appropriate potency assessment is often missing. Reports on functional heterogeneity of MSPCs created additional uncertainty regarding donor and organ/source selection. We established a robust immunomodulation potency assay based on pooling responder leukocytes to minimize individual immune response variability. Comparing various MSPCs revealed significant potency inconsistency and generally diminished allo-immunosuppression compared to dose-dependent inhibition of mitogenesis. Gamma-irradiation to block unintended MSPC proliferation did not prohibit chondrogenesis and osteogenesis in vivo, indicating the need for alternative safety strategies.

• Publication year

  2015

• Venue

  Stem cell research & therapeutics

• Publication date

  2015-12-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/s13287-015-0233-8PMID 26620155PMCID 4666276
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Gamma-irradiation does not block chondrogenesis or osteogenesis in vivo in mesenchymal stem/progenitor cells.

  Confidence 0.93

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• Comparing mesenchymal stem/progenitor cells reveals substantial potency inconsistency and generally weaker allo-immunosuppression than dose-dependent inhibition of mitogenesis.

  Confidence 0.94

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• Pooling responder leukocytes reduces individual immune-response variability in the immunomodulation potency assay.

  Confidence 0.97

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review

• allo-immunosuppression

  immune phenomenon

  Suppression of an allogeneic immune response by mesenchymal stem/progenitor cells.

  Aliases: alloimmunosuppression

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• chondrogenesis

  differentiation process

  The differentiation process by which cells form cartilage-like tissue.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• dose-dependent inhibition of mitogenesis

  functional readout

  A proliferation readout measuring reduction of mitogen-driven cell division as a functional response.

  Aliases: mitogenesis inhibition

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• gamma-irradiation

  treatment

  An irradiation treatment applied to mesenchymal stem/progenitor cells to prevent unintended proliferation.

  Aliases: irradiation

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• immunomodulation potency assay

  assay

  An assay used to measure the immune-modulatory potency of mesenchymal stem/progenitor cells.

  Aliases: potency assay

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• mesenchymal stem/progenitor cells

  cell type

  Multipotent stromal cells examined here as therapeutic cell products with immunomodulatory activity.

  Aliases: MSPCs

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• osteogenesis

  differentiation process

  The differentiation process by which cells form bone tissue.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review
• pooled responder leukocytes

  cell population

  A combined responder leukocyte population used to reduce person-to-person variability in the assay.

  Aliases: pooled leukocytes

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) review

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