Mesenchymal stromal cells (MSCs) are non-hematopoietic cells present in various tissues and organs. They possess profound immunomodulatory and regenerative properties, which have attracted their use in cellular and regenerative therapies. Hundreds of clinical trials are ongoing to test their utility as a cellular therapy for acute and chronic degenerative and inflammatory disorders. MSCs display excellent safety profiles and are well tolerated in patients. Although regulatory authorities approved their use in some inflammatory conditions, e.g. Graft-versus-Host Disease and Perianal Fistula in Crohn’s Disease, MSC-based therapy is currently exhibiting considerable uncertainty due to contradictory clinical efficacy, likely resulting from variations in MSC products and clinical indications being tested and insufficient clinical potency assessment. At this juncture, it is crucial to evaluate next-generation cell therapy manufacturing and profiling strategies to achieve more consistent and sustainable clinical efficacy.
In this Research Topic, we aim to collect Original Research and Review articles that address strategies for improved manufacturing, potency, and mechanism of action (MoA) assessment of next-generation MSC therapies, to improve their clinical efficacy.
We welcome the submission of manuscripts focusing on, but not limited to, the following subtopics:
1. Innovative strategies to improve functionality: Strategies to enhance the functionalities of MSCs including approaches such as cytokine and metabolic prelicensing, genetic modifications with CRISPR or viral vectors, unique culture conditions, and innovative cell surface modifications.
2. Next-generation manufacturing procedures: Improvement in defined media formulations, and novel technologies for cell expansion, cell harvesting and enumeration, cryopreservation and thawing, and integrated assessment of cell yield vs. functional performance.
3. Advanced potency testing analysis: Potency analysis of MSCs includes functional cellular assays, cell product profiling with genomics, secretomics, metabolomics, proteomics, and Raman spectroscopy, if possible under particular consideration of GMP accessible/compliant readouts.
4. Humanized in vivo and in vitro model systems: Testing the in vivo efficacy of human MSCs in humanized animals or in vitro model systems without cross-species interference, such as human organ-on-chip (OoC) devices. Comparative analysis and modeling of optimal dose and delivery of cells.
5. Advanced biomaterials for boosting efficacy: Investigation of natural and synthetic biomaterials and identifying their effect on MSC functionality. Innovative strategies on the utilization of biomaterials in conjunction with MSCs to enhance the efficacy of cellular therapy.
6. Understanding in vivo biodistribution and fate: Novel strategies and technologies to optimize the in vivo fate, biodistribution, persistence and specific tissue/organ targeting of MSCs and modeling of optimal cell dose to achieve the best therapeutic effect.
7. MSC-derived exosomes and extracellular vesicles: Novel strategies for manufacturing exosomes and extracellular vesicles from MSCs and assessing their therapeutic value. Improving the functionality of MSC-derived exosomes and their application in cellular therapy.
8. Synergistic and antagonistic factors that modulate efficacy: Emphasis on host milieu including cytokines and growth factors, cellular microenvironment, treatment regimen with other drugs (example: immunosuppressants, pain relievers, etc.), host genetics, and polymorphisms.
9. Relevance to immune system / immune system cross-talk. Biomarkers, in vitro and in vivo mechanisms of immune crosstalk that may be indicative of MSCs therapeutic potency in specific clinical indications and pathological contexts specific to their mode of delivery.
Mesenchymal stromal cells (MSCs) are non-hematopoietic cells present in various tissues and organs. They possess profound immunomodulatory and regenerative properties, which have attracted their use in cellular and regenerative therapies. Hundreds of clinical trials are ongoing to test their utility as a cellular therapy for acute and chronic degenerative and inflammatory disorders. MSCs display excellent safety profiles and are well tolerated in patients. Although regulatory authorities approved their use in some inflammatory conditions, e.g. Graft-versus-Host Disease and Perianal Fistula in Crohn’s Disease, MSC-based therapy is currently exhibiting considerable uncertainty due to contradictory clinical efficacy, likely resulting from variations in MSC products and clinical indications being tested and insufficient clinical potency assessment. At this juncture, it is crucial to evaluate next-generation cell therapy manufacturing and profiling strategies to achieve more consistent and sustainable clinical efficacy.
In this Research Topic, we aim to collect Original Research and Review articles that address strategies for improved manufacturing, potency, and mechanism of action (MoA) assessment of next-generation MSC therapies, to improve their clinical efficacy.
We welcome the submission of manuscripts focusing on, but not limited to, the following subtopics:
1. Innovative strategies to improve functionality: Strategies to enhance the functionalities of MSCs including approaches such as cytokine and metabolic prelicensing, genetic modifications with CRISPR or viral vectors, unique culture conditions, and innovative cell surface modifications.
2. Next-generation manufacturing procedures: Improvement in defined media formulations, and novel technologies for cell expansion, cell harvesting and enumeration, cryopreservation and thawing, and integrated assessment of cell yield vs. functional performance.
3. Advanced potency testing analysis: Potency analysis of MSCs includes functional cellular assays, cell product profiling with genomics, secretomics, metabolomics, proteomics, and Raman spectroscopy, if possible under particular consideration of GMP accessible/compliant readouts.
4. Humanized in vivo and in vitro model systems: Testing the in vivo efficacy of human MSCs in humanized animals or in vitro model systems without cross-species interference, such as human organ-on-chip (OoC) devices. Comparative analysis and modeling of optimal dose and delivery of cells.
5. Advanced biomaterials for boosting efficacy: Investigation of natural and synthetic biomaterials and identifying their effect on MSC functionality. Innovative strategies on the utilization of biomaterials in conjunction with MSCs to enhance the efficacy of cellular therapy.
6. Understanding in vivo biodistribution and fate: Novel strategies and technologies to optimize the in vivo fate, biodistribution, persistence and specific tissue/organ targeting of MSCs and modeling of optimal cell dose to achieve the best therapeutic effect.
7. MSC-derived exosomes and extracellular vesicles: Novel strategies for manufacturing exosomes and extracellular vesicles from MSCs and assessing their therapeutic value. Improving the functionality of MSC-derived exosomes and their application in cellular therapy.
8. Synergistic and antagonistic factors that modulate efficacy: Emphasis on host milieu including cytokines and growth factors, cellular microenvironment, treatment regimen with other drugs (example: immunosuppressants, pain relievers, etc.), host genetics, and polymorphisms.
9. Relevance to immune system / immune system cross-talk. Biomarkers, in vitro and in vivo mechanisms of immune crosstalk that may be indicative of MSCs therapeutic potency in specific clinical indications and pathological contexts specific to their mode of delivery.
