Microcapsules engineered to support mesenchymal stem cell (MSC) survival and proliferation enable long-term retention of MSCs in infarcted myocardium

Blocki, Anna; Beyer, Sven; Dewavrin, Jean Yves; Goralczyk, Anna Grazyna; Wang, Yingting; Peh, Priscilla; Ng, Michael; Moonshi, Shehzahdi S.; Vuddagiri, Susmitha; Raghunath, Michael; Martinez, Eliana C.; Bhakoo, Kishore

doi:10.1016/j.biomaterials.2015.02.075

Cited by 92 publications

(83 citation statements)

References 55 publications

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“…Increased LV function and reduced scar size were noted only in the animals treated with encapsulated MSCs, which were associated with better retention and survival of transplanted cells. Blocki et al showed that intramyocardial transplantation of MSC encapsulated in agarose supplemented with collagen type I, fibrin and dextran sulphate resulted in increased myocardial cell retention compared to bare MSCs . In another study, human adipose tissue MSCs were encapsulated in genipin‐cross‐linked alginate‐chitosan microcapsules and transplanted to the infarcted rats .…”

Section: Discussionmentioning

confidence: 99%

“…The cells are embedded in semi‐permeable biodegradable matrix, which is freely permeable to oxygen, nutrients and signalling molecules, and helps maintain cell survival and function . Encapsulation effectively attenuates cell injury by physically separating the cells from antibodies and phagocytes, and decreasing biological losses of cells, especially after allo‐ or xenogeneic transplantation . In addition, encapsulation decreases early vascular washout of the encased cells, because the capsule diameter typically lies in the range of 150‐300 μm and exceeds the diameter of microvessels .…”

Section: Introductionmentioning

confidence: 99%

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Non‐inferiority of microencapsulated mesenchymal stem cells to free cells in cardiac repair after myocardial infarction: A rationale for using paracrine factor(s) instead of cells

Карпов

Puzanov

Ивкин

et al. 2019

Int J Experimental Path

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Summary A major translational barrier to the use of stem cell (SC)‐based therapy in patients with myocardial infarction (MI) is the lack of a clear understanding of the mechanism(s) underlying the cardioprotective effect of SCs. Numerous paracrine factors from SCs may account for reduction in infarct size, but myocardial salvage associated with transdifferentiation of SCs into vascular cells as well as cardiomyocyte‐like cells may be involved too. In this study, bone marrow‐derived rat mesenchymal SC (MSCs) were microencapsulated in alginate preventing viable cell release while supporting their secretory phenotype. The hypothesis on the key role of paracrine factors from MSCs in their cardioprotective activity was tested by comparison of the effect of encapsulated vs free MSCs in the rat model of MI. Intramyocardial administration of both free and encapsulated MSCs after MI caused reduction in scar size (12.1 ± 6.83 and 14.7 ± 4.26%, respectively, vs 21.7 ± 6.88% in controls, P = 0.015 and P = 0.03 respectively). Scar size was not different in animals treated with free and encapsulated MSC (P = 0.637). These data provide evidence that MSC‐derived growth factors and cytokines are crucial for cardioprotection elicited by MSC. Administration of either free or encapsulated MSCs was not arrhythmogenic in non‐infarcted rats. The consistency of our data with the results of other studies on the major role of MSC secretome components in cardiac protection further support the theory that the use of live, though encapsulated, cells for MI therapy may be replaced with heart‐targeted‐sustained delivery of growth factors/cytokines.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Non‐inferiority of microencapsulated mesenchymal stem cells to free cells in cardiac repair after myocardial infarction: A rationale for using paracrine factor(s) instead of cells

Карпов

Puzanov

Ивкин

et al. 2019

Int J Experimental Path

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“…However, due to the relatively small size of microcapsules, there are rarely concerns regarding adequate transport of oxygen and nutrient to the cells that other hydrogel techniques might encounter . Several polymers have been used for such microcapsules, including extracellular matrix proteins, PLGA, alginate, fibrinogen, and chitosan among several others. Specifically, Paul et al recently used alginate microcapsules to encapsulate genetically modified human adipose‐derived stem cells .…”

Section: Boosting Stem Cell Therapy With Engineered Biomaterialsmentioning

confidence: 99%

Engineered Biomaterials to Enhance Stem Cell‐Based Cardiac Tissue Engineering and Therapy

Hasan

Waters

Roula

et al. 2016

Macromolecular Bioscience

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Cardiovascular disease is a leading cause of death worldwide. Since adult cardiac cells are limited in their proliferation, cardiac tissue with dead or damaged cardiac cells downstream of the occluded vessel does not regenerate after myocardial infarction. The cardiac tissue is then replaced with nonfunctional fibrotic scar tissue rather than new cardiac cells, which leaves the heart weak. The limited proliferation ability of host cardiac cells has motivated investigators to research the potential cardiac regenerative ability of stem cells. Considerable progress has been made in this endeavor. However, the optimum type of stem cells along with the most suitable matrix-material and cellular microenvironmental cues are yet to be identified or agreed upon. This review presents an overview of various types of biofunctional materials and biomaterial matrices, which in combination with stem cells, have shown promises for cardiac tissue replacement and reinforcement. Engineered biomaterials also have applications in cardiac tissue engineering, in which tissue constructs are developed in vitro by combining stem cells and biomaterial scaffolds for drug screening or eventual implantation. This review highlights the benefits of using biomaterials in conjunction with stem cells to repair damaged myocardium and give a brief description of the properties of these biomaterials that make them such valuable tools to the field.

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“…According to a recent report early, high-dose, intravenous MSC administration should be preferred [32] . Alternative approaches represent the direct intraarterial injection to improve target cell-load [45], local scaffold-assisted delivery to favour cell viability and proliferation at the target site and diminish spreading of cells to have high loco-regional effects [46] or cell encapsulation to allow for systemic administration but with improved cell survival through a protective 'cell coating' [47,48]. Despite all these approaches, the ideal therapeutic dosage of MSCs for a given application remains unknown.…”

Section: Routes Of Administrationmentioning

confidence: 99%

Premise and promise of mesenchymal stem cell-based therapies in clinical vascularized composite allotransplantation

Schweizer

Gorantla

Plock

2015

Current Opinion in Organ Transplantation

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PURPOSE OF REVIEW Over the past decade, clinical vascularized composite allotransplantation (VCA) has enabled functional and quality of life restoration in a wide range of indications secondary to devastating tissue loss. However, the spectre of toxicity and long-term complications of chronic immunosuppression has curtailed the momentum of VCA. This study summarizes the literature evidence behind successful mesenchymal stem cell (MSC)-based cell therapies highlighting their multipronged immunomodulatory, restorative and regenerative characteristics with special emphasis towards VCA applications. RECENT FINDINGS Experimental and clinical studies in solid organs and VCA have confirmed that MSCs facilitate immunosuppression-free allograft survival or tolerance, stimulate peripheral nerve regeneration, attenuate ischaemia-reperfusion injury, and improve tissue healing after surgery. It has been hypothesized that MSC-induced long-term operational tolerance in experimental VCA is mediated by induction of mixed donor-specific chimerism and regulatory T-cell mechanisms. All these characteristics of MSCs could thus help expand the scope and clinical feasibility of VCA. SUMMARY Cellular therapies, especially those focusing on MSCs, are emerging in solid organ transplantation including VCA. Although some clinical trials have begun to assess the effects of MSCs in solid organ transplantation, much scientific domain remains uncharted, especially for VCA. Purpose of review Over the past decade, clinical vascularized composite allotransplantation (VCA) has enabled functional and quality of life restoration in a wide range of indications secondary to devastating tissue loss. However, the spectre of toxicity and long-term complications of chronic immunosuppression has curtailed the momentum of VCA. This study summarizes the literature evidence behind successful mesenchymal stem cell (MSC)-based cell therapies highlighting their multipronged immunomodulatory, restorative and regenerative characteristics with special emphasis towards VCA applications. Recent findingsExperimental and clinical studies in solid organs and VCA have confirmed that MSCs facilitate immunosuppression-free allograft survival or tolerance, stimulate peripheral nerve regeneration, attenuate ischaemia-reperfusion injury, and improve tissue healing after surgery. It has been hypothesized that MSCinduced long-term operational tolerance in experimental VCA is mediated by induction of mixed donorspecific chimerism and regulatory T-cell mechanisms. All these characteristics of MSCs could thus help expand the scope and clinical feasibility of VCA. SummaryCellular therapies, especially those focusing on MSCs, are emerging in solid organ transplantation including VCA. Although some clinical trials have begun to assess the effects of MSCs in solid organ transplantation, much scientific domain remains uncharted, especially for VCA.

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Microcapsules engineered to support mesenchymal stem cell (MSC) survival and proliferation enable long-term retention of MSCs in infarcted myocardium

Cited by 92 publications

References 55 publications

Non‐inferiority of microencapsulated mesenchymal stem cells to free cells in cardiac repair after myocardial infarction: A rationale for using paracrine factor(s) instead of cells

Non‐inferiority of microencapsulated mesenchymal stem cells to free cells in cardiac repair after myocardial infarction: A rationale for using paracrine factor(s) instead of cells

Engineered Biomaterials to Enhance Stem Cell‐Based Cardiac Tissue Engineering and Therapy

Premise and promise of mesenchymal stem cell-based therapies in clinical vascularized composite allotransplantation

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