Human stem cell-based three-dimensional microtissues for advanced cardiac cell therapies

Emmert, Maximilian Y.; Wolint, Petra; Wickboldt, Nadine; Gemayel, Gino; Weber, Benedikt; Brokopp, Chad E.; Boni, Alessandro; Falk, Volkmar; Bosman, Alexis; Jaconi, Marisa; Hoerstrup, Simon P.

doi:10.1016/j.biomaterials.2013.04.034

Cited by 67 publications

(52 citation statements)

References 54 publications

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“…48 A transcatheter-based electromechanical mapping-guided intramyocardial transplantation of A-MSC aggregates in the porcine heart showed the improved survival and tissue integration, whereas single-cell injection displayed low level and random distribution. 20,21 Thus, in vitro preconditioning MSCs in aggregates may be an effective strategy to enhance cell survival and the secretion of trophic factors in vivo for myocardial disease therapy.…”

Section: Msc Aggregates Enhanced Cardiac Transplantationmentioning

confidence: 99%

“…5,18,19 The benefits of cell aggregation has also been shown in preclinical studies, in which intramyocardial transplantation of the 3D A-MSC and BM-MSC aggregates in a porcine model improved cell retention, survival, and integration. 20,21 Similarly, transplantation of synovial MSC aggregates promoted cartilage tissue regeneration in a rabbit model and enhanced meniscus tissue regeneration effectively in rats. 22,23 Thus, there is a growing interest to better understand the mechanism of MSC 3D aggregation, its impact on cell properties, and its feasibility in therapeutic applications.…”

mentioning

confidence: 99%

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Three-Dimensional Aggregates of Mesenchymal Stem Cells: Cellular Mechanisms, Biological Properties, and Applications

Sart

Tsai

et al. 2014

Tissue Engineering Part B: Reviews

331

362

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Mesenchymal stem cells (MSCs) are primary candidates in cell therapy and tissue engineering and are being tested in clinical trials for a wide range of diseases. Originally isolated and expanded as plastic adherent cells, MSCs have intriguing properties of in vitro self-assembly into three-dimensional (3D) aggregates reminiscent of skeletal condensation in vivo. Recent studies have shown that MSC 3D aggregation improved a range of biological properties, including multilineage potential, secretion of therapeutic factors, and resistance against ischemic condition. Hence, the formation of 3D MSC aggregates has been explored as a novel strategy to improve cell delivery, functional activation, and in vivo retention to enhance therapeutic outcomes. This article summarizes recent reports of MSC aggregate self-assembly, characterization of biological properties, and their applications in preclinical models. The cellular and molecular mechanisms underlying MSC aggregate formation and functional activation are discussed, and the areas that warrant further investigation are highlighted. These analyses are combined to provide perspectives for identifying the controlling mechanisms and refining the methods of aggregate fabrication and expansion for clinical applications.

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Section: Msc Aggregates Enhanced Cardiac Transplantationmentioning

confidence: 99%

mentioning

confidence: 99%

Three-Dimensional Aggregates of Mesenchymal Stem Cells: Cellular Mechanisms, Biological Properties, and Applications

Sart

Tsai

et al. 2014

Tissue Engineering Part B: Reviews

331

362

View full text Add to dashboard Cite

show abstract

“…The aggregation of cells into 3D-MTs prior to transplantation might be an improvement for current cardiac regenerative strategies [52,53]. Indeed, 3D-MTs are thought to enhance cell retention and engraftment thanks to the production of extracellular matrix.…”

Section: Combination Therapiesmentioning

confidence: 99%

Cardiac Regenerative Medicine: The Potential of a New Generation of Stem Cells

Cambria

Steiger

Günter

et al. 2016

Transfus Med Hemother

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Cardiac stem cell therapy holds great potential to prompt myocardial regeneration in patients with ischemic heart disease. The selection of the most suitable cell type is pivotal for its successful application. Various cell types, including crude bone marrow mononuclear cells, skeletal myoblast, and hematopoietic and endothelial progenitors, have already advanced into the clinical arena based on promising results from different experimental and preclinical studies. However, most of these so-called first-generation cell types have failed to fully emulate the promising preclinical data in clinical trials, resulting in heterogeneous outcomes and a critical lack of translation. Therefore, different next-generation cell types are currently under investigation for the treatment of the diseased myocardium. This review article provides an overview of current stem cell therapy concepts, including the application of cardiac stem (CSCs) and progenitor cells (CPCs) and lineage commitment via guided cardiopoiesis from multipotent cells such as mesenchymal stem cells (MSCs) or pluripotent cells such as embryonic and induced pluripotent stem cells. Furthermore, it introduces new strategies combining complementary cell types, such as MSCs and CSCs/CPCs, which can yield synergistic effects to boost cardiac regeneration.

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“…Microtissues are scaffold-free tissue-engineered spheroids generated via hanging drop technique. These microstructures are reproducible with different cell types like CPCs, bone marrow- and adipose tissue-derived MSCs [4] and have been tested in a pilot study on infarcted porcine models exhibiting promising results [12]. Other methods currently investigated for increasing cell retention in the infarcted areas include i) the combination of single cell suspensions with nanoparticles loaded with functional agents [13], ii) the injection of a compact mixture of cells pre-cultured in hydrogels [14], or iii) the injection of cell-free hydrogels functionalized with paracrine mediators [15].…”

Section: Regenerative Technologies For Heart Failurementioning

confidence: 99%

“…In this context, regenerative medicine can be considered as innovative and valid alternative. The identification of progenitor cardiac cells within the adult human heart [1] encouraged the enthusiasm for cell-based regenerative therapies [2,3,4]. Moreover, the evidence that exogenous cells injected in the myocardium could minimally promote the formation of functional contractile tissue in the scarred areas provided an important contribution in directing the preclinical research towards the investigation of possible new treatments [5].…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Regenerative Technologies: Update and Future Outlook

Mallone¹,

Weber²,

Hoerstrup³

2016

Transfus Med Hemother

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In the effort of improving treatment for cardiovascular disease (CVD), scientists struggle with the lack of the regenerative capacities of finally differentiated cardiovascular tissues. In this context, the advancements in regenerative medicine contributed to the development of cell-based therapies as well as macro- and micro-scale tissue-engineering technologies. The current experimental approaches focus on different regenerative strategies including a broad spectrum of techniques such as paracrine-based stimulation of autologous cardiac stem cells, mesenchymal cell injections, 3D microtissue culture techniques and vascular tissue-engineering methods. These potential next-generation strategies are leading the way to a revolution in addressing CVD, and numerous studies are now undertaken to assess their therapeutic value. With this review, we provide an update on the current research directions, on their major challenges, limitations, and achievements.

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Human stem cell-based three-dimensional microtissues for advanced cardiac cell therapies

Cited by 67 publications

References 54 publications

Three-Dimensional Aggregates of Mesenchymal Stem Cells: Cellular Mechanisms, Biological Properties, and Applications

Three-Dimensional Aggregates of Mesenchymal Stem Cells: Cellular Mechanisms, Biological Properties, and Applications

Cardiac Regenerative Medicine: The Potential of a New Generation of Stem Cells

Cardiovascular Regenerative Technologies: Update and Future Outlook

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