Inter- and Intra-donor variability in bone marrow-derived mesenchymal stromal cells: implications for clinical...

Area of Science:

• Cellular Biology
• Regenerative Medicine
• Immunology

Background:

• Mesenchymal stromal cells (MSCs) are promising for treating inflammatory and vascular diseases.
• Bone marrow-derived MSCs (BM-MSCs) were found safe for moderate-to-severe acute respiratory distress syndrome (ARDS) in a Phase 2a trial.
• This study analyzed MSC doses from the START trial, considering variations between donors and collection times.

Purpose of the Study:

• To correlate MSC properties with patient plasma biomarkers relevant to ARDS outcomes.
• To investigate inter- and intra-donor variability in MSC characteristics.
• To assess the functional impact of MSCs on endothelial barrier permeability.

Main Methods:

• Evaluated MSC donor lots for viability, growth, metabolism, and surface/protein markers.
• Assessed immunomodulatory capacity and endothelial cell permeability regulation.
• Correlated MSC properties with patient plasma biomarkers (ANG-2, Protein C) post-transfusion.

Main Results:

• MSC marker expression and endothelial barrier protection were consistent across donor lots.
• Significant inter- and intra-donor variability was found in other in vitro assays.
• Patient plasma ANG-2 and Protein C levels correlated with MSC viability in a donor-dependent manner.

Conclusions:

• Donor-dependent (inter-) and collection-dependent (intra-) effects influence patient biomarker expression.
• Highlights the importance of considering MSC donor variability in therapeutic applications.
• Suggests a need for standardized MSC characterization for ARDS treatment.