Adipose-derived mesenchymal stem cells: Source-dependent heterogeneity, translational challenges, and emerging precision strategies

Table 2 Major translational challenges in adipose-derived mesenchymal stem cell-based therapy and potential strategies to address them

Challenge	Main problem	Potential strategy	Ref.
Donor heterogeneity	Major variability in phenotype and function	Source-aware donor screening	[5,6,8,12,37]
Depot-specific variability	Different depots yield distinct ADSCs	Match source to therapeutic indication	[1,3,4,37]
Regional variability	Subcutaneous depots are not equivalent	Improve anatomical precision in tissue collection	[1,5]
Isolation inconsistency	Isolation methods alter downstream cell behavior	Standardize processing workflows	[37]
Culture-induced drift	Serum, oxygen, and culture format reshape phenotype	Use defined media and standardized culture systems	[6,14,15,29]
Cryopreservation variability	Freezing and thawing affect cell quality	Optimize banking and post-thaw validation	[30,46]
Lack of potency assays	Functional release criteria remain unclear	Develop source-aware potency markers	[6,30,47,50]
Incomplete molecular stratification	Bulk analyses miss functional subpopulations	Apply single-cell and multi-omics profiling	[52-55]
Secretome heterogeneity	Secretome products are highly source- and process-dependent	Standardize production and characterization	[56-60]
Manufacturing inconsistency	Scale-up and reproducibility remain limited	Introduce source-aware manufacturing and QC systems	[54,63,65]
Limited trial stratification	Clinical trials often insufficiently stratify source/product features	Incorporate source-related variables into trial design	[50,52,61,62,64]

ADSCs: Adipose-derived mesenchymal stem cells; QC: Quality control.