Breastmilk-Derived Mesenchymal Stem Cells In Vitro Are Likely to Be Mediated Through Epithelial–Mesenchymal Transition

Breastmilk had been identified to possess several nonimmunological cell components including stem cells. However, as rightly mentioned in the correspondence, isolation of mesenchymal stem cells (MSCs) from breastmilk and its marker characterization are uncertain until today. One of the authors had already reported in her article ¹ that breastmilk possesses various integral cellular components with scanty MSCs in fresh colostrums. However, there is no accumulating evidence or supporting studies (published articles) to prove that breastmilk possesses no MSCs under culture conditions.

The cultured breastmilk cells are heterogeneous initially and attain homogeneous MSC-like cells upon subsequent passages. This was also supported by Sani et al. ² who specified that increasing number of MSCs would be obtained upon passages. Furthermore, there are evidences to suggest that growth factors such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are secreted by MSCs.^3,4 Hence, we had cultured breastmilk extensively and had carried out the growth factor assay to prove that these mesenchymal stem-like cells that have been developed upon subsequent passages secrete these growth factors. ⁵ Since this article involves only the study of growth factor, we had not further discussed on MSCs here.

However, to further confirm our hypothesis, we had addressed this issue by in vitro culturing and characterizing the breastmilk-derived cells for hematopoietic, mesenchymal, and epithelial markers, and so on to confirm that breastmilk does not possess inherent MSCs but attains mesenchyml stem-like cells upon subsequent passages, which here might be due to epithelial-mesenchymal transition (EMT), as reported by Hassiotou et al. ⁶ This was further supported by Patki et al. ⁷ with the positive expression of breastmilk-cultured cells for E-cadherin. Hence, we say that these mesenchymal stem-like cells may grow through EMT, in which they express both epithelial and mesenchymal markers. This was also accepted by Foteini et al. in their recent correspondence addressed to you.

Thus, we strongly believe that breastmilk develops fibroblastic plastic-adherent mesenchymal stem-like cells upon subsequent passages and these cells have secreted the growth factors. Further in-depth characterization of cultured breastmilk-derived mesenchymal cells and its mediated mechanisms would give new insight into several unexplored applications.