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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Spoerer, Thomas M. Larey, Andrew M. Asigri, Winifred Daga, Kanupriya R. Marklein, Ross A. |
| Abstract | Background While mesenchymal stromal cell (MSC) therapies show promise for treating several indications due to their regenerative and immunomodulatory capacity, clinical translation has yet to be achieved due to a lack of robust, scalable manufacturing practices. Expansion using undefined fetal bovine serum (FBS) or human platelet lysate contributes to MSC functional heterogeneity and limits control of product quality. The need for tunable and consistent media has thus motivated development of chemically defined media (CDM). However, CDM development strategies are often limited in their screening approaches and unable to reliably assess the impact of media on MSC function, often neglecting high-level interactions of media components such as growth factors. Given that MSC morphology has been shown to predict their immunomodulatory function, we employed a high throughput screening (HTS) approach to elucidate effects of growth factor compositions on MSC phenotype and proliferation in a custom CDM. Methods HTS of eight growth factors in a chemically defined basal medium (CDBM) was conducted via a two-level, full factorial design using adipose-derived MSCs. Media hits were identified leveraging cell counts and morphological profiles. After validating phenotypic responses to hits across multiple donors, MSCs were cultured over three passages in serum-containing medium (SCM) and CDM hits and assayed for growth and immunomodulatory function. Finally, growth factor concentrations in one hit were further refined, and MSC growth and function was assessed. Results Our HTS approach led to the discovery of several CDM formulations that enhanced MSC proliferation and demonstrated wide ranging impacts on MSC immunomodulation. Notably, two hits showed 4X higher growth compared to SCM over 3 passages without compromising immunomodulatory function. Refinement of one CDM hit formulation reduced growth factor concentrations by as much as 90% while maintaining superior growth and similar function to SCM. Altogether, distinct MSC morphological profiles observed from screening were indicative of differential MSC quality that allowed for development of an effective CDM for MSC expansion. Conclusions Overall, this highlights how our HTS approach led to the development of CDM formulations for robust MSC expansion and serves as a generalizable tool for improvement of MSC manufacturing processes. |
| Related Links | https://stemcellres.biomedcentral.com/counter/pdf/10.1186/s13287-025-04206-8.pdf |
| Ending Page | 15 |
| Page Count | 15 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17576512 |
| DOI | 10.1186/s13287-025-04206-8 |
| Journal | Stem Cell Research & Therapy |
| Issue Number | 1 |
| Volume Number | 16 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2025-03-07 |
| Access Restriction | Open |
| Subject Keyword | Stem Cells Cell Biology Regenerative Medicine Tissue Engineering Biomedical Engineering and Bioengineering Mesenchymal stromal cells Defined medium Immunomodulation High throughput screening Morphology Cell therapy Regenerative Medicine/Tissue Engineering |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Biochemistry, Genetics and Molecular Biology Molecular Medicine |
| Journal Impact Factor | 7.1/2023 |
| 5-Year Journal Impact Factor | 7.9/2023 |
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