Abstract
BackgroundHuman mesenchymal stem cells are a strong candidate for cell therapies owing to their regenerative potential, paracrine regulatory effects, and immunomodulatory activity. Yet, their scarcity, limited expansion potential, and age-associated functional decline restrict the ability to consistently manufacture large numbers of safe and therapeutically effective mesenchymal stem cells for routine clinical applications. To overcome these limitations and advance stem cell treatments using mesenchymal stem cells, researchers have recently derived mesenchymal progenitors from human-induced pluripotent stem cells. Human-induced pluripotent stem cell-derived progenitors resemble adult mesenchymal stem cells in morphology, global gene expression, surface antigen profile, and multi-differentiation potential, but unlike adult mesenchymal stem cells, it can be produced in large numbers for every patient. For therapeutic applications, however, human-induced pluripotent stem cell-derived progenitors must be produced without animal-derived components (xeno-free) and in accordance with Good Manufacturing Practice guidelines.MethodsIn the present study we investigate the effects of expanding mesodermal progenitor cells derived from two human-induced pluripotent stem cell lines in xeno-free medium supplemented with human platelet lysates and in a commercial high-performance Good Manufacturing Practice-compatible medium (Unison Medium).ResultsThe results show that long-term culture in xeno-free and Good Manufacturing Practice-compatible media somewhat affects the morphology, expansion potential, gene expression, and cytokine profile of human-induced pluripotent stem cell-derived progenitors but supports cell viability and maintenance of a mesenchymal phenotype equally well as medium supplemented with fetal bovine serum.ConclusionsThe findings support the potential to manufacture large numbers of clinical-grade human-induced pluripotent stem cell-derived mesenchymal progenitors for applications in personalized regenerative medicine.Graphical abstract
Highlights
The ability to treat diseases via administration of stem cells is becoming a plausible therapeutic option [2]
Expansion potential, and viability To investigate the effects of different media on cell phenotype, the morphology, expansion potential, and viability of 1013A-mesenchymal progenitor (MP) and BC1-MP cells were studied from P6 to P15
Starting at P7, cells cultured in the AllegroTM medium begin displaying a more elongated morphology compared to cells cultured in media supplemented with either fetal bovine serum (FBS) or HPL, which instead preserve their initial morphology (Fig. 1 and Additional file 2: Figure S1)
Summary
The ability to treat diseases via administration of stem cells is becoming a plausible therapeutic option [2]. Human adult MSCs can be isolated from many tissues, including bone marrow, periosteum, fat, skeletal muscle, and synovial fluid, as well as from the cord blood, umbilical cord, and placenta [15] In recent years, these cells have been used for the treatment of hematopoietic [24], cardiovascular [23], and autoimmune diseases [34] and for the repair of traumatic bone and cartilage injuries [10], with numerous clinical trials conducted worldwide every year [38]. Human mesenchymal stem cells are a strong candidate for cell therapies owing to their regenerative potential, paracrine regulatory effects, and immunomodulatory activity Their scarcity, limited expansion potential, and age-associated functional decline restrict the ability to consistently manufacture large numbers of safe and therapeutically effective mesenchymal stem cells for routine clinical applications. Human-induced pluripotent stem cell-derived progenitors must be produced without animal-derived components (xeno-free) and in accordance with Good Manufacturing Practice guidelines
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