Cell-Based Therapies: The Nonresponder

Caplan, Arnold I.

doi:10.1002/sctm.18-0074

Cited by 30 publications

(31 citation statements)

References 20 publications

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“…Despite this, only two drugs, TEMCELL ® , for the treatment of acute graft-versus-host disease, and Alofisel ® (Darvadstrocel), for the treatment of fistulae in Crohn’s disease, have been approved by regulatory agencies. For various reasons, MSCs approval as a drug is proving elusive[ 161 , 162 ] and, from the outside, it might seem that the field is in a period of stagnation.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells secretome: The cornerstone of cell-free regenerative medicine

González-González

García-Sánchez

Dotta

et al. 2020

WJSC

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Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells secretome: The cornerstone of cell-free regenerative medicine

González-González

García-Sánchez

Dotta

et al. 2020

WJSC

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“…In addition, the quantity of μ FAT was chosen based on previous reports [9], but the proportion between cells and tissue hardly corresponds to the physiological ratio. Another limitation is given by the possible influence of patients' characteristics on the activity of μ FAT, which was not taken into account in the present work while it may indeed identify a fraction of individuals who are nonresponders to the μ FAT treatment due to pathology or adipose tissue-specific features [74] and thus representing a source of bias.…”

Section: Discussionmentioning

confidence: 99%

Autologous Microfragmented Adipose Tissue Reduces the Catabolic and Fibrosis Response in an In Vitro Model of Tendon Cell Inflammation

Viganò

Lugano

Orfei

et al. 2019

Stem Cells International

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Background Mesenchymal stem cells (MSCs) emerged as a promising therapy for tendon pathologies. Microfragmented adipose tissue (μFAT) represents a convenient autologous product for the application of MSC-based therapies in the clinical setting. In the present study, the ability of μFAT to counteract inflammatory processes induced by IL-1β on human tendon cells (TCs) was evaluated. Methods Cell viability and proliferation were evaluated after 48 hours of transwell coculture of TCs and autologous μFAT in the presence or absence of IL-1β. Gene expression of scleraxis, collagen type I and type III, metalloproteinases-1 and -3, and cyclooxygenase-2 was evaluated by real-time RT-PCR. The content of VEGF, IL-1Ra, TNFα, and IL-6 was evaluated by ELISA. Results IL-1β-treated TCs showed augmented collagen type III, metalloproteases, and cyclooxygenase-2 expression. μFAT was able to reduce the expression of collagen type III and metalloproteases-1 in a significant manner, and at the same time, it enhanced the production of VEGF, IL-1Ra, and IL-6. Conclusions In this in vitro model of tendon cell inflammation, the paracrine action of μFAT, exerted by anti-inflammatory molecules and growth factors, was able to inhibit the expression of fibrosis and catabolic markers. Then, these results suggest that the application of μFAT may represent an effective conservative or adjuvant therapy for the treatment of tendon disorders.

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“…The nonresponders among patients receiving MSCs appear to be a reflection of a combination of factors; the MSC production method for therapy, the cells’ metabolic activity, the delivered dose, the stage of the disease, and the status and/or genetic receptivity of the patient. 155,156 Given this complexity, it has become apparent to many researchers that the MSCs used for therapy must be carefully produced and properly “tuned” for the intended therapy. The tuned MSCs should be optimized for the required medicinal response and for the patients’ capacity to respond, as best this is understood.…”

Section: Optimizing Mscs For Therapeutic Purposes: Tuning Their Outputmentioning

confidence: 99%

Mesenchymal stem cell perspective: cell biology to clinical progress

et al. 2019

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The terms MSC and MSCs have become the preferred acronym to describe a cell and a cell population of multipotential stem/progenitor cells commonly referred to as mesenchymal stem cells, multipotential stromal cells, mesenchymal stromal cells, and mesenchymal progenitor cells. The MSCs can differentiate to important lineages under defined conditions in vitro and in limited situations after implantation in vivo. MSCs were isolated and described about 30 years ago and now there are over 55,000 publications on MSCs readily available. Here, we have focused on human MSCs whenever possible. The MSCs have broad anti-inflammatory and immune-modulatory properties. At present, these provide the greatest focus of human MSCs in clinical testing; however, the properties of cultured MSCs in vitro suggest they can have broader applications. The medical utility of MSCs continues to be investigated in over 950 clinical trials. There has been much progress in understanding MSCs over the years, and there is a strong foundation for future scientific research and clinical applications, but also some important questions remain to be answered. Developing further methods to understand and unlock MSC potential through intracellular and intercellular signaling, biomedical engineering, delivery methods and patient selection should all provide substantial advancements in the coming years and greater clinical opportunities. The expansive and growing field of MSC research is teaching us basic human cell biology as well as how to use this type of cell for cellular therapy in a variety of clinical settings, and while much promise is evident, careful new work is still needed.

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Cell-Based Therapies: The Nonresponder

Cited by 30 publications

References 20 publications

Mesenchymal stem cells secretome: The cornerstone of cell-free regenerative medicine

Mesenchymal stem cells secretome: The cornerstone of cell-free regenerative medicine

Autologous Microfragmented Adipose Tissue Reduces the Catabolic and Fibrosis Response in an In Vitro Model of Tendon Cell Inflammation

Mesenchymal stem cell perspective: cell biology to clinical progress

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