Table 2 A number of study areas are suggested where new results could improve the understanding of MSC basic science and/or clinical therapies.

From: Mesenchymal stem cell perspective: cell biology to clinical progress

Challenges in the field

Opportunities/solutions

Defining the “MSC” and specific MSC populations for therapy

Reconcile lineage tracing/genetic results with phenotypic/functional studies of cultured MSCs

Tissue-resident MSCs

Omics-based approaches, rigorous (and tissue relevant) functional testing to define similarities and differences

Decrease in in vivo MSCs with age

Augment with ex vivo produced MSCs

Intra/inter-population heterogeneity

Longitudinal culture assays, genetic tagging, bar coding

Use of autologous vs. allogeneic MSCs

Test in parallel in vitro and in vivo, disease relevance

MSCs for tissue replacement

Fate priming w/cytokines and culture conditions, substrates (rigid or flexible, etc.), smart scaffolds, engineered tissue

MSCs into injured tissue

Assays for altered expression of factors and exosome contents of in vitro cultured MSCs placed in the in vivo and injured tissue setting

Lack of engraftment

Preconditioning for in vivo metabolism and hypoxia to prevent apoptosis; scaffolds as delivery vehicles, recovery from freezing prior to infusion

Dosing regimens

Single bolus, or repeated or escalating doses

Delivery methods

Direct, local, or systemic—optimize for tissue and disease type

Disease-specific treatments

“Tune” MSCs using biologics, select for defining traits via potency assays, CLIP scale

Cell therapy release assays

Not universal but designed for the specific disease, target tissue, and patient population