“Cell-Free Therapeutics” from Components Secreted by Mesenchymal Stromal Cells as a Novel Class of Biopharmaceuticals

Regenerative medicine is a fast growing multidisciplinary field aiming at the regeneration or replacement of damaged cells, tissues, or organs. Adult multipotent mesenchymal stromal cells (MSCs) are often used as a principal therapeutic tool in this field. Along with differentiation potency, MSCs secrete a wide spectrum of paracrine factors and extracellular vesicles participating in tissue repair and regeneration. Thus, for injuries that require trophic stimulation, cell survival support, and/or resident stem cells activation to be restored, one can apply MSC-conditioned medium, a combination of products and extracellular vesicles in cell culture growth medium, secreted by MSC. It could mediate most of beneficial regenerative effects of MSC without possible side effects of using MSC themselves. However, before the clinical application of this promising biopharmaceutical, several issues such as manufacturing protocols, quality control, and others must be addressed. Subsequently, we highlight the questions considering donor material variability, manufacturing, cell culture medium and auxiliary components selection, and potency tests development

Unveiling Mesenchymal Stromal Cells’ Organizing Function in Regeneration

Regeneration is a fundamental process attributed to the functions of adult stem cells. In the last decades, delivery of suspended adult stem cells is widely adopted in regenerative medicine as a leading means of cell therapy. However, adult stem cells cannot complete the task of human body regeneration effectively by themselves as far as they need a receptive microenvironment (the niche) to engraft and perform properly. Understanding the mechanisms underlying mammalian regeneration leads us to an assumption that improved outcomes of cell therapy require a specific microenvironment that is generated in damaged areas prior to stem cell delivery. To a certain extent, it may be achieved by the delivery of mesenchymal stromal cells (MSCs), not in dispersed form, but rather in self-organized cell sheets (CS) ⁻ tissue-like structures comprised of viable cells and microenvironment components: extracellular matrix and soluble factors deposited in the matrix. In this review, we highlight the potential role of MSCs as regeneration organizers and speculate that this function emerges in CS. This concept shifts our understanding of the therapeutic mechanism underlying a widely known CS-based delivery method for regenerative medicine