Lineage Heterogeneity: Functional Differences in Mesenchymal Stromal Cells

In previous editions, we explored the general characteristics of Mesenchymal Stromal Cells (MSC), as well as the role of the secretome and exosomes in their therapeutic applications. One of the topics that generates the greatest interest among both physicians and patients is selecting the most appropriate MSC source for clinical use. Umbilical cord or Wharton’s jelly-derived MSCs are often favored due to their wider research base; however, as discussed, various sources are viable, including adipose …

What is the secretomic profile, and why does it matter?

Although MSCs share common morphological features, they exhibit significant differences in their secretomic profiles—the collection of bioactive molecules they secrete and through which they mediate therapeutic effects. These variations directly influence efficacy, as each source produces a unique combination of cytokines, growth factors, anti-apoptotic proteins, and extracellular vesicles. Understanding these distinctions is essential to selecting the right MSC source for each clinical application.

Scientific evidence on differences between sources

MSCs can migrate to sites of injury and actively participate in tissue repair by interacting with the damaged microenvironment and releasing their secretome. This includes soluble factors (chemokines, cytokines, growth factors) and extracellular vesicles such as exosomes, which play a central role in their therapeutic effects (Eleuteri & Fierabracci, 2019).

Shin et al. (2021) compared expression levels of key therapeutic proteins such as TIMP, VEGF, CSF, HGF, TGF-β, IL-6, and PDGF, all linked to angiogenesis. These were predominantly found in secretomes from placenta and Wharton’s jelly. Matrix metalloproteinases involved in tissue remodeling and development were abundant in bone marrow and placental MSCs. Meanwhile, anti-apoptotic proteins like PPIA, PPIB, and PPIC were identified in adipose tissue, Wharton’s jelly, and placenta. Cytokines and immunoregulatory factors such as IL-6, IL-11, LIF, ICAM, and CXCL were especially prominent in Wharton’s jelly-derived secretomes.

Other studies highlight the therapeutic differences among MSC sources:
– Mead et al. (2014): Dental pulp-derived MSCs showed greater neuroprotective and neuritogenic potential than bone marrow or adipose tissue MSCs.
– Pires et al. (2016): Bone marrow secretomes were most effective at reducing oxidative stress; cord and adipose MSCs were better for minimizing excitotoxicity.
– Talwadekar et al. (2015): Placenta-derived MSCs showed superior immune regulatory function compared to cord-derived MSCs from the same donor.
– Wolbank et al. (2007): Dose-dependent immunomodulatory effects were observed in MSCs from amniotic tissue and adipose tissue.

Clinical applications by MSC source

– Placenta / Wharton’s Jelly: Tissue regeneration, angiogenesis, and immunomodulation
– Bone marrow: Oxidative stress control and tissue remodeling
– Adipose tissue: Immune regulation and anti-apoptotic activity
– Dental pulp: Neuroprotection and neurite regeneration

Clinical implementation challenges

These findings underline the need for unbiased, comparative studies tailored to specific diseases and based on human clinical data. Most evidence still comes from animal models, limiting direct applicability. Additionally, the cell culture environment—oxygen levels, nutrients, stimuli—can alter the secretome, highlighting the need to standardize conditions and protocols for future clinical scalability.

Conclusion and clinical perspective

Despite considerable progress, the research and clinical application of MSCs continues to evolve. What remains clear is that to offer effective treatments, it is essential to understand not only the differences among MSC sources but also the individual characteristics of each patient and their pathology.

At Baja Regenerative, we are committed to the responsible, evidence-based use of Mesenchymal Stromal Cells. If you’d like to learn more about the optimal source for your patients or explore our therapeutic options, contact us and receive professional guidance from our clinical and scientific team.

References

• Zhao, Q., Larios, K., Naaldijk, Y., Sherman, L., Chemerinski, A., Okereke, K., Rameshwar, P., Lemenze, A., Douglas, N. C., & Morelli, S. S. (2023). Mesenchymal Stem Cell Secretome Alters Gene Expression and Upregulates Motility of Human Endometrial Stromal Cells. Reproduction, 166(2), 161–174. https://doi.org/10.1530/REP-22-0485
• Shin, S., Lee, J., Kwon, Y., Park, K.-S., Jeong, J.-H., Choi, S.-J., Bang, S. I., Chang, J. W., & Lee, C. (2021). Comparative proteomic analysis of the mesenchymal stem cells secretome from adipose, bone marrow, placenta and Wharton’s jelly. International Journal of Molecular Sciences, 22(2), 845. https://doi.org/10.3390/ijms22020845​
• Eleuteri, S., & Fierabracci, A. (2019). Insights into the secretome of mesenchymal stem cells and its potential applications. International Journal of Molecular Sciences, 20(18), 4597. https://doi.org/10.3390/ijms20184597
• Mead, B., Logan, A., Berry, M., Leadbeater, W., & Scheven, B. A. (2014). Neuroprotección y neuritogénesis mediadas por mecanismos paracrinos de células ganglionares de la retina axotomizadas por células madre de la pulpa dental humana: Comparación con células madre mesenquimales derivadas de la médula ósea y tejido adiposo humano. PLoS ONE, 9(1), e109305. https://doi.org/10.1371/journal.pone.0109305
• Pires, A. O., Mendes-Pinheiro, B., Teixeira, F. G., Anjo, S. I., Ribeiro-Samy, S., Gómez, E. D., Serra, C. S., Silva, N. A., Manadas, B., Sousa, N., et al. (2016). Revelando las diferencias del secretoma de las células madre mesenquimales de la médula ósea humana, las células madre derivadas del tejido adiposo y las células perivasculares del cordón umbilical humano: un análisis proteómico. Desarrollo de Células Madre, 25, 1073-1083. https://doi.org/10.1016/j.stem.2016.04.004
• Talwadekar, M. D., Kale, V. P., & Limaye, L. S. (2015). Las células madre mesenquimales derivadas de la placenta poseen mejores propiedades inmunorreguladoras en comparación con sus contrapartes derivadas del cordón umbilical: un estudio de muestras pareadas. Scientific Reports, 5, 15784. https://doi.org/10.1038/srep15784
• Wolbank, S., Peterbauer, A., Fahrner, M., Hennerbichler, S., van Griensven, M., Stadler, G., Redl, H., & Gabriel, C. (2007). Efecto inmunomodulador dosis-dependiente de células madre humanas de membrana amniótica: Una comparación con células madre mesenquimales humanas de tejido adiposo. Tissue Engineering, 13(5), 1173–1183. https://doi.org/10.1089/ten.2006.0458

Author: Biol. Carlos D. Reyes Padilla