Setting the Stage for NextGen MSCs

hiPSC-derived iMSCs as an advanced therapeutically active cell resource for regenerative medicine

Mesenchymal stem cells (MSCs) are being assessed for ameliorating the severity of graft-versus-host disease, autoimmune conditions, musculoskeletal injuries and cardiovascular diseases. While most of these clinical therapeutic applications require substantial cell quantities, the number of MSCs that can be obtained initially from a single donor remains limited. The utility of MSCs derived from human-induced pluripotent stem cells (hiPSCs) has been shown in recent pre-clinical studies. Since adult MSCs have limited capability regarding proliferation, the quantum of bioactive factor secretion and their immunomodulation ability may be constrained. The hiPSC-derived MSCs (iMSCs) are transpiring as an attractive source of MSCs because during the reprogramming process, cells undergo rejuvination, exhibiting better cellular vitality. The autologous iMSCs could be considered as an inexhaustible source of MSCs that could be used to meet the unmet clinical needs.

Human-induced PSC-derived MSCs are reported to be superior when compared to the adult MSCs regarding cell proliferation, immunomodulation, cytokines profiles, microenvironment modulating exosomes and bioactive paracrine factors secretion. Strategies, such as derivation and propagation of iMSCs in chemically defined culture conditions and use of footprint-free safer reprogramming strategies have contributed towards the development of clinically relevant cell types.

Presently, only initial studies are reported on preclinical applications of iMSCs. Hence, long-term, multicentric, pre-clinical and clinical studies are required for accurate prediction of iMSCs for the translational purpose. The recent development of non-viral-based generation of iPSCs might pave the way for considering iPSCs as a suitable candidate for biotherapeutics. Newer technologies without viral transgene, such as chemicals, plasmids and recombinant protein-based approaches might augment the clinical utilization of these safe iPSCs. The low efficiency of iPSCs generation might be a severe-debilitating factor to consider iPSCs/iMSCs for translational applications. Hence, more research needs to be focused on scaling and optimizing the quality of iPSCs.

The invention of cellular reprogramming of adult cells from the terminally differentiated state of iPSCs, with the help of transcription factors, biological factors and small molecules, opens up a large window of opportunity in the field of regenerative medicine. By incorporating the advantages of both iPSCs and MSCs, the resulting iMSCs are emerging as a novel stem cell population. The iMSCs generated from iPSCs successfully exhibited all the fundamental criteria for defining the MSC population based on the existing knowledge. Data indicates that iMSCs can be used as a promising alternative strategy for treatment of various immune-mediated diseases.

Although, the concept of iMSCs is at its nascent stage, recent studies nevertheless provided the proof of concept that functional iMSCs could be successfully generated from iPSCs that exhibit robust proliferation and differentiation potential – which could be used for tissue repair and engineering applications. The development of iMSCs offers promise of patient-specific, cost-efficient and batch to batch consistency. Presently, the scope of iMSCs is limited to the pre-clinical utility for tissue engineering-based treatment approaches. Further pre-clinical and clinical studies are required before scaling it towards routine clinical utility.

For more information on hiPSC-derived iMSCs, join me at Cell & Gene Therapy Bioprocessing & Commercialization event this October in Boston. And for special savings, be sure to use the VIP code “B16188BLOG” – See you this October.



About the author: Justin Gaines is a Boston-based drug discovery professional and biotech enthusiast. During his tenures he has remained active within the biomedical engineering and regenerative medicine sectors, and has remained an avid proponent of bringing together the Boston life science community. He is currently leading the Bio Pharma Networking Group across the North East – a professional life science and healthcare community spanning 6K members. View his last contribution to KNect365 Bioprocessing here.



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