Cell secretome based drug substances in regenerative medicine: when regulatory affairs meet basic science

Beer, Lucian; Mildner, Michael; Ankersmit, Hendrik Jan

doi:10.21037/atm.2017.03.50

Cited by 86 publications

(66 citation statements)

References 18 publications

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“…Their content depends on the surrounding environment and may change upon cell stimulation. EVs include microvesicles (MVs) (100-1000 nm), exosomes (EXs) (40-100 nm), and apoptotic bodies (1-5 μm) [80,[88][89][90]. Once EVs reach their target sites, they interact and attach to the target cell surface, where they either remain attached, become internalized by the target cell via fusion with the cell membrane as well as via the endocytotic pathway to discharge their content intracellularly, or become detached from the cell surface after completing their action [89,91].…”

Section: Dental Stem/progenitor Cells (Dental Mscs)mentioning

confidence: 99%

Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications

Moshy

Radwan

Rady

et al. 2020

Stem Cells International

108

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Regenerative medicine literature has proposed mesenchymal stem/progenitor cell- (MSC-) mediated therapeutic approaches for their great potential in managing various diseases and tissue defects. Dental MSCs represent promising alternatives to nondental MSCs, owing to their ease of harvesting with minimally invasive procedures. Their mechanism of action has been attributed to their cell-to-cell contacts as well as to the paracrine effect of their secreted factors, namely, secretome. In this context, dental MSC-derived secretome/conditioned medium could represent a unique cell-free regenerative and therapeutic approach, with fascinating advantages over parent cells. This article reviews the application of different populations of dental MSC secretome/conditioned medium in in vitro and in vivo animal models, highlights their significant implementation in treating different tissue’ diseases, and clarifies the significant bioactive molecules involved in their regenerative potential. The analysis of these recent studies clearly indicate that dental MSCs’ secretome/conditioned medium could be effective in treating neural injuries, for dental tissue regeneration, in repairing bone defects, and in managing cardiovascular diseases, diabetes mellitus, hepatic regeneration, and skin injuries, through regulating anti-inflammatory, antiapoptotic, angiogenic, osteogenic, and neurogenic mediators.

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Section: Dental Stem/progenitor Cells (Dental Mscs)mentioning

confidence: 99%

Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications

Moshy

Radwan

Rady

et al. 2020

Stem Cells International

108

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“…The paracrine effects of MSCs, firstly described by Gnecchi et al [27], are due to numerous secreted elements collectively referred to as the secretome [28]. The secretome consists of all factors actively or passively released from cells; it contains soluble products composed of a proteic soluble fraction (mostly growth factors and cytokines) and a vesicular component, extracellular vesicles (EVs), which transfer proteins, lipids, and genetic material to recipient cells [29]. The MSC-derived secretome is very tissue-and/or individual cell-specific and is subject to fluctuations related to physiological states or pathological conditions.…”

Section: Introductionmentioning

confidence: 99%

Paracrine Mechanisms of Mesenchymal Stromal Cells in Angiogenesis

Maacha

Sidahmed²,

Jacob

et al. 2020

Stem Cells International

176

131

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The role of the mesenchymal stromal cell- (MSC-) derived secretome is becoming increasingly intriguing from a clinical perspective due to its ability to stimulate endogenous tissue repair processes as well as its effective regulation of the immune system, mimicking the therapeutic effects produced by the MSCs. The secretome is a composite product secreted by MSC in vitro (in conditioned medium) and in vivo (in the extracellular milieu), consisting of a protein soluble fraction (mostly growth factors and cytokines) and a vesicular component, extracellular vesicles (EVs), which transfer proteins, lipids, and genetic material. MSC-derived secretome differs based on the tissue from which the MSCs are isolated and under specific conditions (e.g., preconditioning or priming) suggesting that clinical applications should be tailored by choosing the tissue of origin and a priming regimen to specifically correct a given pathology. MSC-derived secretome mediates beneficial angiogenic effects in a variety of tissue injury-related diseases. This supports the current effort to develop cell-free therapeutic products that bring both clinical benefits (reduced immunogenicity, persistence in vivo, and no genotoxicity associated with long-term cell cultures) and manufacturing advantages (reduced costs, availability of large quantities of off-the-shelf products, and lower regulatory burden). In the present review, we aim to give a comprehensive picture of the numerous components of the secretome produced by MSCs derived from the most common tissue sources for clinical use (e.g., AT, BM, and CB). We focus on the factors involved in the complex regulation of angiogenic processes.

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“…As a result, several authors have implied that the secretion of paracrine factors is the major MSC therapeutic mechanism involved in skin ulcer repair [79,[122][123][124]. factors, soluble proteins, chemokines, cytokines, glycosaminoglycans, free nucleic acids, lipids, and extracellular vesicles (apoptotic bodies, microparticles and exosomes) [125].…”

Section: Msc-based Therapy For Chronic Wound Healingmentioning

confidence: 99%

Function and Therapeutic Potential of Mesenchymal Stem Cells and Their Acellular Derivatives on Non-Healing Chronic Skin Ulcers

Solarte¹,

Becerra-Bayona²,

Sánchez-Aranguren³

et al. 2018

J Stem Cell Res Ther

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Non-healing chronic skin ulcers are considered a major biological, psychological, and financial burden for both patients and health systems. Multidisciplinary endeavors are required to address this refractory disease, in order to find definitive solutions that lead to improved living conditions. Diabetes, venous stasis, arterial insufficiency, pressure and radiation are common risk factors associated with chronic wounds. Unfortunately, the cured state for these wounds has a high relapse rate, which adversely affects the patient's quality of life. Nevertheless, advances on regenerative medicine have allowed the development of cell-based therapies that promote wound healing by increasing cell migration and differentiation. Particularly, mesenchymal stem cells (MSCs) and their acellular derivatives have emerged as an attractive therapeutic agent in various diseases, including chronic skin ulcers, due to their role in immunomodulation and tissue regeneration. In this review discusses the characteristics of MSCs as well as their regenerative properties and their action mechanisms on wound healing. Finally, the perspectives of MSCs and their acellular derivatives in clinical chronic skin ulcer therapy are also explored.

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Cell secretome based drug substances in regenerative medicine: when regulatory affairs meet basic science

Cited by 86 publications

References 18 publications

Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications

Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications

Paracrine Mechanisms of Mesenchymal Stromal Cells in Angiogenesis

Function and Therapeutic Potential of Mesenchymal Stem Cells and Their Acellular Derivatives on Non-Healing Chronic Skin Ulcers

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