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

Stem Cell Research & Therapy, 2015 · DOI: 10.1186/s13287-015-0233-8 · Published: November 9, 2015

Simple Explanation

Mesenchymal stem/progenitor cells (MSPCs) have the ability to modulate the immune system, which has led to many clinical trials. There's a need for potency assessment because of functional heterogeneity of MSPCs, which creates uncertainty regarding donor and organ/source selection. A new robust immunomodulation potency assay was established based on pooling responder leukocytes to minimize individual immune response variability.

Study Duration

Not specified

Participants

MSPCs from five random human BM, white adipose tissue (WAT) and umbilical cord (UC) donors were analyzed individually or as a pool.

Evidence Level

Not specified

Key Findings

1
Significant potency inconsistency and diminished allo-immunosuppression in MSPCs compared to dose-dependent inhibition of mitogenesis.
2
Gamma-irradiation to block unintended MSPC proliferation did not prohibit chondrogenesis and osteogenesis in vivo, indicating the need for alternative safety strategies.
3
All MSPCs displayed significant dose-dependent suppression of T-cell mitogenesis.

Research Summary

The study introduces a robust potency assay using inhibition of pooled polyclonal T-lymphocyte proliferation after mitogen or antibody stimulation and due to allo-antigen-driven mixed leukocyte reaction. Significant differences were observed between individual donors compared to their organotypic reference when testing freshly thawed versus cultured individual donor-derived MSPC inhibitory effectiveness. Irradiation did not influence the immunosuppressive potency of MSPCs, but caution is advised as irradiated BM-MSPCs maintained their capacity to differentiate along chondrogenic and osteogenic lineages in vivo.

Practical Implications

Donor Selection

The potency assay can be included in the release criteria of advanced cell therapy medicinal products to better select MSPC donors.

Process Optimization

The assay can help optimize cell processing methodology, specifically regarding off-the-shelf use versus rescue culture of cryopreserved MSPCs.

Safety Measures

Alternative strategies for blocking unintended differentiation need to be identified because gamma irradiation was insufficient to prohibit chondrogenic and osteogenic MSPC differentiation.

Study Limitations

1
Incomplete mechanistic insight into MSPC mode of action.
2
Lack of predictive biomarkers.
3
Functional MSPC heterogeneity within a given tissue and between different organs.

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