Healing parenchyma with mesenchyme: exploring a new therapeutic paradigm for site-specific tissue repair

Abstract

[eng] Nature heals damaged specialized tissues by mending torn tissues, feeding hungry tissues, holding injurious processes and replacing damaged units, thanks to a developmentally defined group of cells -the stromal cells- comprised by a heterogeneous population of fibroblasts, endothelial cells, tissue resident mononuclear and progenitor cells. Stromal cells share common essential functions and processes, a common mesenchymal ancestry and early developmental stages, as they remain located within the three-dimensional perivascular structure of different tissues. Certainly, the stromal cell functions adapt to resident tissue specificity unique properties holds and such specificities have been constitutively determined by the surrounding parenchyma, not being present during earlier differentiation stages. However, stromal mesenchymal cells lose their tissue-specific functions following tissue dissociation when cultured in-vitro under non-specific media conditions; they regain their tissue-specific functions in response to their own specific culture media or when returned to their initial tissue source (orthotopic implantation); and express different tissue-specific functions when exposed to other tissue-specific media conditions or after heterotopic implantation. Therefore, if such reparative functions were retained by stromal cells after tissue dissociation, cell selection and concentration: Would these stromal cells express their essential reparative properties when exchanged among different muscle-skeletal tissues? Would they display reparative functions immediately upon engraftment or after in-vivo reprogramming into tissue-specific supporting cells? If instead, these stromal cells did not express their essential reparative functions when delivered heterotopically: Would it be a feasible method to then obtain tissue specific stromal cells which could be reliably engrafted and exert a therapeutic effect following orthotopic implantation?