Viability and functionality of mesenchymal stromal cells loaded on collagen microspheres and incorporated into plasma clots for orthopaedic application: Effect of storage conditions

Wittig, Olga; Diaz‐Solano, Dylana; Cardier, José E.

doi:10.1016/j.injury.2018.04.005

Cited by 15 publications

(11 citation statements)

References 24 publications

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“…MSCs are currently one of the most used cells in preclinical and clinical trials in humans and animals [35,36]. However, there is substantial variability in clinical outcomes that limit MSC use and regulatory approval.…”

Section: Discussionmentioning

confidence: 99%

A multicenter experience using adipose-derived mesenchymal stem cell therapy for cats with chronic, non-responsive gingivostomatitis

et al. 2020

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Background The ability of mesenchymal stem cells (MSCs) to modulate immune responses inspired a series of clinical trials addressing oral mucosal inflammation. We previously reported on the safety and efficacy of fresh, allogeneic and autologous, adipose-derived mesenchymal stem cells (ASCs) to treat feline gingivostomatitis (FCGS), an oral mucosal inflammatory disease that shares similarities with human oral lichen planus. Methods To meet clinical demand and goals for future commercialization, we determined the feasibility of shipping fresh ASCs to distant clinics and extended our pilot studies to expand safety and efficacy data for shipped and non-shipped ASCs in a cohort of 18 FCGS cats enrolled locally and at a few different locations within the USA. Results We found that ASCs retained their viability, phenotype, and function after shipment. ASCs administered systemically resulted in a 72% positive response rate, identical to that noted in our previous studies. Cats that responded to ASC therapy had a significant decrease in circulating globulin concentration and histological evidence of decreased CD3+ T cells and CD20+ B cells in the oral mucosa. Responder cats also had significantly decreased percentages of CD8lo cells in blood prior to and at 3 months post-ASC therapy. CD8lo cells may serve as a potential “predictor” for response to systemic ASC therapy. Conclusion Fresh feline ASCs can be successfully shipped and administered to cats with FCGS. ASCs modulate the immune response and demonstrate efficacy for chronic oral mucosal inflammatory lesions that are characterized by CD8+ T cell inflammation and T cell activation. FCGS is a potentially useful naturally occurring large animal model of human oral inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

A multicenter experience using adipose-derived mesenchymal stem cell therapy for cats with chronic, non-responsive gingivostomatitis

et al. 2020

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“…One of the main challenges for using stem cells in clinical applications is to ensure their survival and functionality during delivery from the laboratory to the administration site [40]. Although cryopreservation is the best choice for long-term storage of MSCs, these cells may be maintained in a non-frozen state for short-term shipment.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Autologous Adipose-Derived Stem Cells for the Treatment of Liver Disease

Gardin

Ferroni

Bellin

et al. 2018

IJMS

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Currently, the most effective therapy for liver diseases is liver transplantation, but its use is limited by organ donor shortage, economic reasons, and the requirement for lifelong immunosuppression. Mesenchymal stem cell (MSC) transplantation represents a promising alternative for treating liver pathologies in both human and veterinary medicine. Interestingly, these pathologies appear with a common clinical and pathological profile in the human and canine species; as a consequence, dogs may be a spontaneous model for clinical investigations in humans. The aim of this work was to characterize canine adipose-derived MSCs (cADSCs) and compare them to their human counterpart (hADSCs) in order to support the application of the canine model in cell-based therapy of liver diseases. Both cADSCs and hADSCs were successfully isolated from adipose tissue samples. The two cell populations shared a common fibroblast-like morphology, expression of stemness surface markers, and proliferation rate. When examining multilineage differentiation abilities, cADSCs showed lower adipogenic potential and higher osteogenic differentiation than human cells. Both cell populations retained high viability when kept in PBS at controlled temperature and up to 72 h, indicating the possibility of short-term storage and transportation. In addition, we evaluated the efficacy of autologous ADSCs transplantation in dogs with liver diseases. All animals exhibited significantly improved liver function, as evidenced by lower liver biomarkers levels measured after cells transplantation and evaluation of cytological specimens. These beneficial effects seem to be related to the immunomodulatory properties of stem cells. We therefore believe that such an approach could be a starting point for translating the results to the human clinical practice in future.

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“…Considering the potential of UC-MSC to differentiate to osteogenic lineages, we finally sought to test whether UC-MSC cultured on 3D-collagen scaffolds could enhance their capacity to form bone-like structures. We first evaluated whether MSC were able to induce bone-like structures in a previously established model of scaffolds based on collagen microbeads [29]. To that end, we preconditioned two groups of UC-MSC (passage 5) for 3 days in the presence of proosteogenic medium (UC-MSC/OM) or proendothelial differentiation medium (UC-MSC/EM).…”

Section: Resultsmentioning

confidence: 99%

Strategy for the Generation of Engineered Bone Constructs Based on Umbilical Cord Mesenchymal Stromal Cells Expanded with Human Platelet Lysate

Silva-Cote¹,

Cruz-Barrera²,

Cañas-Arboleda³

et al. 2019

Stem Cells International

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Umbilical cord mesenchymal stromal cells (UC-MSC) are promising candidates for cell therapy due to their potent multilineage differentiation, enhanced self-renewal capacity, and immediate availability for clinical use. Clinical experience has demonstrated satisfactory biosafety profiles and feasibility of UC-MSC application in the allogeneic setting. However, the use of UC-MSC for bone regeneration has not been fully established. A major challenge in the generation of successful therapeutic strategies for bone engineering lies on the combination of highly functional proosteogenic MSC populations and bioactive matrix scaffolds. To address that, in this study we proposed a new approach for the generation of bone-like constructs based on UC-MSC expanded in human platelet lysate (hPL) and evaluated its potential to induce bone structures in vivo. In order to obtain UC-MSC for potential clinical use, we first assessed parameters such as the isolation method, growth supplementation, microbiological monitoring, and cryopreservation and performed full characterization of the cell product including phenotype, growth performance, tree-lineage differentiation, and gene expression. Finally, we evaluated bone-like constructs based on the combination of stimulated UC-MSC and collagen microbeads for in vivo bone formation. UC-MSC were successfully cultured from 100% of processed UC donors, and efficient cell derivation was observed at day 14 ± 3 by the explant method. UC-MSC maintained mesenchymal cell morphology, phenotype, high cell growth performance, and probed multipotent differentiation capacity. No striking variations between donors were recorded. As expected, UC-MSC showed tree-lineage differentiation and gene expression profiles similar to bone marrow- and adipose-derived MSC. Importantly, upon osteogenic and endothelial induction, UC-MSC displayed strong proangiogenic and bone formation features. The combination of hPL-expanded MSC and collagen microbeads led to bone/vessel formation following implantation into an immune competent mouse model. Collectively, we developed a high-performance UC-MSC-based cell manufacturing bioprocess that fulfills the requirements for human application and triggers the potency and effectivity of cell-engineered scaffolds for bone regeneration.

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Viability and functionality of mesenchymal stromal cells loaded on collagen microspheres and incorporated into plasma clots for orthopaedic application: Effect of storage conditions

Cited by 15 publications

References 24 publications

A multicenter experience using adipose-derived mesenchymal stem cell therapy for cats with chronic, non-responsive gingivostomatitis

A multicenter experience using adipose-derived mesenchymal stem cell therapy for cats with chronic, non-responsive gingivostomatitis

Therapeutic Potential of Autologous Adipose-Derived Stem Cells for the Treatment of Liver Disease

Strategy for the Generation of Engineered Bone Constructs Based on Umbilical Cord Mesenchymal Stromal Cells Expanded with Human Platelet Lysate

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