Prolonged survival of transplanted stem cells after ischaemic injury via the slow release of pro-survival peptides from a collagen matrix

Lee, Andrew S.; Inayathullah, Mohammed; Lijkwan, Maarten A.; Zhao, Xin; Sun, Wenchao; Park, Su‐Jin; Hong, Wan Xing; Parekh, Mansi; Malkovskiy, Andrey V.; Lau, Edward; Qin, Xulei; Pothineni, Venkata Raveendra; Sánchez-Freire, Verónica; Zhang, Wendy Y.; Kooreman, Nigel G.; Ebert, Antje; Chan, Charles K.; Nguyen, Patricia K.; Jayakumar, R.; Wu, Joseph C.

doi:10.1038/s41551-018-0191-4

Cited by 77 publications

(55 citation statements)

References 36 publications

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“…One promising strategy to improve MSC therapies is biomaterial encapsulation. Various biomaterial formulations have been shown to support and direct MSC phenotype, in both preclinical and clinical settings (10)(11)(12)(13)(14)(15). However, these strategies generally involve encapsulation of MSCs in bulk hydrogels that preclude their administration in an intravenous (i.v.)…”

mentioning

confidence: 99%

Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation

Mao

Özkale

Shah

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

154

104

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Mesenchymal stem cell (MSC) therapies demonstrate particular promise in ameliorating diseases of immune dysregulation but are hampered by short in vivo cell persistence and inconsistencies in phenotype. Here, we demonstrate that biomaterial encapsulation into alginate using a microfluidic device could substantially increase in vivo MSC persistence after intravenous (i.v.) injection. A combination of cell cluster formation and subsequent cross-linking with polylysine led to an increase in injected MSC half-life by more than an order of magnitude. These modifications extended persistence even in the presence of innate and adaptive immunity-mediated clearance. Licensing of encapsulated MSCs with inflammatory cytokine pretransplantation increased expression of immunomodulatory-associated genes, and licensed encapsulates promoted repopulation of recipient blood and bone marrow with allogeneic donor cells after sublethal irradiation by a ∼2-fold increase. The ability of microgel encapsulation to sustain MSC survival and increase overall immunomodulatory capacity may be applicable for improving MSC therapies in general.

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mentioning

confidence: 99%

Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation

Mao

Özkale

Shah

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

154

104

View full text Add to dashboard Cite

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“…Thus, they are of special interest as a therapeutic approach to prevent adverse LV remodeling [19]. A vast pool of materials have been assessed for this purpose, and range from natural polymers such as myocardial ECM [20], hyaluronate [21], collagen [22], fibrin [23], and alginate [24] to synthetic polymers such as ureido-pyrimidinone-modified poly(ethylene glycol) [25] and poly(N-isopropylacrylamide) [26]. Despite a wide range of preclinical studies with promising outcomes, their translation to the clinic has been limited to a very few hydrogels that have reached final phases of clinical trials.…”

Section: Introductionmentioning

confidence: 99%

A Cell-Free SDKP-Conjugated Self-Assembling Peptide Hydrogel Sufficient for Improvement of Myocardial Infarction

et al. 2020

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Biomaterials in conjunction with stem cell therapy have recently attracted attention as a new therapeutic approach for myocardial infarction (MI), with the aim to solve the delivery challenges that exist with transplanted cells. Self-assembling peptide (SAP) hydrogels comprise a promising class of synthetic biomaterials with cardiac-compatible properties such as mild gelation, injectability, rehealing ability, and potential for sequence modification. Herein, we developed an SAP hydrogel composed of a self-assembling gel-forming core sequence (RADA) modified with SDKP motif with pro-angiogenic and anti-fibrotic activity to be used as a cardioprotective scaffold. The RADA-SDKP hydrogel was intramyocardially injected into the infarct border zone of a rat model of MI induced by left anterior descending artery (LAD) ligation as a cell-free or a cell-delivering scaffold for bone marrow mesenchymal stem cells (BM-MSCs). The left ventricular ejection fraction (LVEF) was markedly improved after transplantation of either free hydrogel or cell-laden hydrogel. This cardiac functional repair coincided very well with substantially lower fibrotic tissue formation, expanded microvasculature, and lower inflammatory response in the infarct area. Interestingly, BM-MSCs alone or in combination with hydrogel could not surpass the cardiac repair effects of the SDKP-modified SAP hydrogel. Taken together, we suggest that the RADA-SDKP hydrogel can be a promising cell-free construct that has the capability for functional restoration in the instances of acute myocardial infarction (AMI) that might minimize the safety concerns of cardiac cell therapy and facilitate clinical extrapolation.

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“…Codelivery of the hiPSC–ECs and hiPSC–SMCs with fibrinogen gel into the porcine model of MI lead to angiogenesis factor‐enriched exosome secretion that significantly improved cardiomyocytes survival and maturation, and contributed to the engraftment and angiogenesis at periscar border zone, which improved functional recovery of myocardium as a consequence. In addition to the codelivery strategy, direct encapsulation of prosurvival peptides in biomaterials was also proved to improve angiogenesis ( Figure ) . Lee et al conjugated peptide analogues of bone morphogenetic protein‐2 (BMP2), erythropoietin (EPO), and fibroblast growth factor‐2 (FGF2) to collagen fibers (Col × D × Pep) via a dendrimer linker to achieve the sustained release of the peptides to delivered cells.…”

Section: Applications Of Advanced Biomaterials For Stem Cell Deliverymentioning

confidence: 99%

Advanced Functional Biomaterials for Stem Cell Delivery in Regenerative Engineering and Medicine

Wang

Rivera‐Bolanos

Jiang

et al. 2019

Adv Funct Materials

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Stem cell-based therapies can potentially regenerate many types of tissues and organs, thereby providing solutions to a variety of diseases and injuries. However, acute cell death, uncontrolled differentiation, and low functional engraftment yields remain critical obstacles for clinical translation. Advanced functional biomaterial scaffolds that can deliver stem cells to the targeted tissues/organs and promote stem cell survival, differentiation, and integration to host tissues may potentially transform the clinical outcome of stem cellbased regenerative therapies. In this review, the authors briefly summarize sources of stem cells for transplantation, present the current state of the art in biomaterial design for stem cell delivery, and provide critical analysis for existing materials. Applications to the cardiovascular, neural, and musculoskeletal systems are highlighted with recent nonclinical studies and clinical trials. The authors also discuss how advances in biomaterials research can contribute to regenerative medicine research and stem cell therapies. application in the clinical setting. These challenges include the manipulation of stem cell fate pre-and post-transplantation and protection of the cells during and after their delivery to the target site. [3] The microenvironment, also referred to as stem cell niche, plays key roles in stem cell fate determination. [4] In vivo, the interplay among complex microenvironmental cues precisely regulate stem cell function so they may undergo self-renewal to maintain the stem cell pool or to undergo differentiation to regenerate tissue. However, the majority of current stem cell transplant strategies in clinical trials use injections with a buffer fluid, which provides insufficient protection and manipulation of cell fate. [5] As a result, the vast majority of transplanted cells die during their delivery or within a short time thereafter. Engineering approaches, especially in the biomaterials field, offer strategies to address the challenges and current limitations of stem cell therapy. Innovative design of biomaterials enables delicate control of their biophysical and biochemical properties, which provides an artificial niche to regulate stem cell functions. Delivery of cells via engineered biomaterial carriers can promote cell survival by reducing the microenvironmental shock (shear stress, inflammation, etc.), improving cell retention by preventing cell leakage and enhancing regenerative responses from delivered cells by manipulating stem cell fate. [6] In this review, we summarize and provide perspective on stem cell sources and the state of the art in the design, fabrication, and application of advanced functional biomaterials for stem cell delivery. We discuss current stem cell phenotypes and the requirements in biomaterial design and fabrication for successful stem cell transplantation. We also highlight recent nonclinical and clinical studies of stem cell therapy in the cardiovascular, neural, and musculoskeletal systems. Lastly, we conclude with an outlo...

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Prolonged survival of transplanted stem cells after ischaemic injury via the slow release of pro-survival peptides from a collagen matrix

Cited by 77 publications

References 36 publications

Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation

Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation

A Cell-Free SDKP-Conjugated Self-Assembling Peptide Hydrogel Sufficient for Improvement of Myocardial Infarction

Advanced Functional Biomaterials for Stem Cell Delivery in Regenerative Engineering and Medicine

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