How do Mesenchymal Stem Cells Repair?

Semedo, Patrícia; Burgos-Silva, Marina; Donizetti-Oliveira, Cassiano; Câmara, Niels Olsen Saraiva

doi:10.5772/17574

Cited by 17 publications

(16 citation statements)

References 153 publications

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“…Increasing evidences have demonstrated that the fraction of administered cells that actually survives upon transplantation, engrafts, differentiates, and provides functional support for tissue regeneration is minimal [7]. Moreover, some beneficial effects have been observed upon administration of factors secreted by MSCs [8]. These observations suggest that the prevalent mechanism by which MSCs exert their contribution to tissue regeneration is mostly associated with their paracrine activity [9–13].…”

Section: Introductionmentioning

confidence: 99%

Towards Therapeutic Delivery of Extracellular Vesicles: Strategies for In Vivo Tracking and Biodistribution Analysis

Rocco¹,

Baldari²,

Toietta³

2016

Stem Cells International

120

101

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Extracellular vesicles (EVs), such as microvesicles and exosomes, are membranous structures containing bioactive material released by several cells types, including mesenchymal stem/stromal cells (MSCs). Increasing lines of evidences point to EVs as paracrine mediators of the beneficial effects on tissue remodeling associated with cell therapy. Administration of MSCs-derived EVs has therefore the potential to open new and safer therapeutic avenues, alternative to cell-based approaches, for degenerative diseases. However, an enhanced knowledge about in vivo EVs trafficking upon delivery is required before effective clinical translation. Only a few studies have focused on the biodistribution analysis of exogenously administered MSCs-derived EVs. Nevertheless, current strategies for in vivo tracking in animal models have provided valuable insights on the biodistribution upon systemic delivery of EVs isolated from several cellular sources, indicating in liver, spleen, and lungs the preferential target organs. Different strategies for targeting EVs to specific tissues to enhance their therapeutic efficacy and reduce possible off-target effects have been investigated. Here, in the context of a possible clinical application of MSC-derived EVs for tissue regeneration, we review the existing strategies for in vivo tracking and targeting of EVs isolated from different cellular sources and the studies elucidating the biodistribution of exogenously administered EVs.

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Section: Introductionmentioning

confidence: 99%

Towards Therapeutic Delivery of Extracellular Vesicles: Strategies for In Vivo Tracking and Biodistribution Analysis

Rocco¹,

Baldari²,

Toietta³

2016

Stem Cells International

120

101

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“…The regenerative mechanisms of the transplanted MSCs in damaged tissues are not fully understood; however, some reports have suggested potential mechanisms including cell fusion, differentiation, and paracrine effects [ 29 , 30 ]. Cell fusion occurs with low frequency but plays an important role in several biological functions, including development, physiology, and disease pathology, and it is classified into two types: homotypic and heterotypic cell fusion [ 16 ]. Homotypic fusion occurs between cells of the same lineage, whereas heterotypic fusion occurs between cells of different lineages [ 31 ].…”

Section: Regeneration Mechanisms Of Transplanted Mscsmentioning

confidence: 99%

“…The study by Devine et al demonstrated that allogeneic MSCs were not rejected and were associated with outcomes similar to those of autologous (self-derived) MSCs in nonhuman primates [ 14 , 15 ]. Consequently, these characteristics make MSCs suitable for therapeutic use, and many preclinical studies of the therapeutic application of MSCs have demonstrated their beneficial effects [ 16 , 17 ]. In addition, one hundred clinical trials using MSCs were ongoing in 2011 [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Cell Adhesion and Long-Term Survival of Transplanted Mesenchymal Stem Cells: A Prerequisite for Cell Therapy

Lee

Choi

Cha

et al. 2015

Oxidative Medicine and Cellular Longevity

218

153

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The literature provides abundant evidence that mesenchymal stem cells (MSCs) are an attractive resource for therapeutics and have beneficial effects in regenerating injured tissues due to their self-renewal ability and broad differentiation potential. Although the therapeutic potential of MSCs has been proven in both preclinical and clinical studies, several questions have not yet been addressed. A major limitation to the use of MSCs in clinical applications is their poor viability at the site of injury due to the harsh microenvironment and to anoikis driven by the loss of cell adhesion. To improve the survival of the transplanted MSCs, strategies to regulate apoptotic signaling and enhance cell adhesion have been developed, such as pretreatment with cytokines, growth factors, and antiapoptotic molecules, genetic modifications, and hypoxic preconditioning. More appropriate animal models and a greater understanding of the therapeutic mechanisms of MSCs will be required for their successful clinical application. Nevertheless, the development of stem cell therapies using MSCs has the potential to treat degenerative diseases. This review discusses various approaches to improving MSC survival by inhibiting anoikis.

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“…MSC differentiation contributes by regenerating damaged tissue, whereas MSC paracrine signaling regulates the local cellular responses to injury. Although, the molecular mechanisms of MSCs involvement in healing response are not yet fully understood, MSC paracrine signaling is thought to be the likely primary mechanism for the beneficial effects of MSCs on injury healing, that is, to reduce inflammation, promote angiogenesis, and induce cell migration and proliferation [62][63][64][65][66][67].…”

Section: Regenerative Potential Of Mscs and Paracrine Activitiesmentioning

confidence: 99%

“…In addition, MSCs have a role in each of the three-stage injury healing responses (inflammatory, proliferative, and remodeling), and their presence supports healthy physiologic functioning towards successful healing. For example, MSCs regulate immune and inflammatory responses, and possess powerful tissue protective and reparative effects through paracrine signaling by releasing biologically active molecules that affect cell migration, proliferation, and survival/remodeling of the cells surrounding the site of injury [62][63][64][65][66][67].…”

Section: Regenerative Potential Of Mscs and Paracrine Activitiesmentioning

confidence: 99%

Rationale for Using Direct Bone Marrow Aspirate as a Proliferant for Regenerative Injection Therapy (Prolotherapy)

Hauser

Eteshola²

2013

TOSCJ

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Adult mesenchymal stem cells (MSCs) obtainable from autologous bone marrow aspirates have generated tremendous interest in the medical and scientific communities in the last two decades and are currently being investigated by a of interested physicians for use in point-of-care stem cell therapies due to their great potential to differentiate into multiple cell lineages such as bone, cartilage, muscle, tendon, and nerve. However, as these stem cells are found in very low numbers in adult tissue, centrifugal concentration or expansion through in vitro culturing has been pursued to obtain higher numbers of efficacious regenerative therapeutic applications. More recently, some physicians and scientists have chosen to explore use for direct injection of un-fractionated, native whole bone marrow aspirate as a strategy in regenerative treatment regimes. This review examines the potential merits and disadvantages of using either concentrated and culture expanded MSCs versus native whole bone marrow aspirate as key proliferant in direct regenerative injection therapy (RIT). Results from a number of published investigations have clearly shown high potential of various deleterious effects on manipulating MSCs obtained from native bone marrow aspirate either by centrifugal forces or expansion through in vitro culturing; moreover, currently used centrifugal concentration techniques do not significantly concentrate MSCs from bone marrow aspirate, thus, defeating the purpose of this manipulative step. On the other hand, preliminary results and observations of using un-fractionated whole bone marrow injection for treatment of various musculoskeletal joint diseases (for example, osteoarthritic joints) suggest that the procedure is safe and potentially efficacious, with no known deleterious effects as yet reported.

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How do Mesenchymal Stem Cells Repair?

Cited by 17 publications

References 153 publications

Towards Therapeutic Delivery of Extracellular Vesicles: Strategies for In Vivo Tracking and Biodistribution Analysis

Towards Therapeutic Delivery of Extracellular Vesicles: Strategies for In Vivo Tracking and Biodistribution Analysis

Cell Adhesion and Long-Term Survival of Transplanted Mesenchymal Stem Cells: A Prerequisite for Cell Therapy

Rationale for Using Direct Bone Marrow Aspirate as a Proliferant for Regenerative Injection Therapy (Prolotherapy)

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