Fast-Degradable Microbeads Encapsulating Human Umbilical Cord Stem Cells in Alginate for Muscle Tissue Engineering

Liu, Jun; Zhou, Hongzhi; Weir, Michael D.; Xu, Hockin H.K.; Chen, Qianming; Trotman, Carroll Ann

doi:10.1089/ten.tea.2011.0658

Cited by 31 publications

(31 citation statements)

References 71 publications

(121 reference statements)

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“…The median particle sizes of TTCP and DCPA were 17 μm and 1 μm, respectively. Chitosan lactate (Halosource, Redmond, WA) was modified with covalently conjugated G 4 RGDSP oligopeptides (Peptides International, Louisville, KY) using carbodiimide chemistry as described previously [10,29,30]. The weight ratio of chitosan/G 4 RGDSP was 1000/12.4.…”

Section: Methodsmentioning

confidence: 99%

Effect of NELL1 gene overexpression in iPSC-MSCs seeded on calcium phosphate cement

et al. 2014

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Human induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) are a promising source of patient-specific stem cells with great regenerative potential. There has been no report on NEL-like protein 1 (NELL1) gene modification of iPSC-MSCs. The objectives of this study were to genetically modify iPSC-MSCs with NELL1 overexpression for bone tissue engineering, and investigate the osteogenic differentiation of NELL1 gene-modified iPSC-MSCs seeded on Arg-Gly-Asp (RGD)-grafted calcium phosphate cement (CPC) scaffold. Cells were transduced with red fluorescence protein (RFP-iPSC-MSCs) or NELL1 (NELL1-iPSC-MSCs) by a lentiviral vector. Cell proliferation on RGD-grafted CPC scaffold, osteogenic differentiation and bone mineral synthesis were evaluated. RFP-iPSC-MSCs stably expressed high levels of RFP. Both the NELL1 gene and NELL1 protein levels were confirmed higher in NELL1-iPSC-MSCs than in RFP-iPSC-MSCs using RT-PCR and Western blot (p < 0.05). Alkaline phosphatase (ALP) activity was increased by 130% by NELL1 overexpression at 14 d (p < 0.05), indicating that NELL1 promoted iPSC-MSC osteogenic differentiation. When seeded on RGD-grafted CPC, NELL1-iPSC-MSCs attached and expanded similarly well to RFP-iPSC-MSCs. At 14 d, runt-related transcription factor 2 (RUNX2) gene level of NELL1-iPSC-MSCs was 2.0-fold that of RFP-iPSC-MSCs. Osteocalcin (OC) level of NELL1-iPSC-MSCs was 3.1-fold that of RFP-iPSC-MSCs (p < 0.05). Collagen type I alpha 1 (COL1A1) gene level of NELL1-iPSC-MSCs was 1.7-fold that of RFP-iPSC-MSCs at 7 d (p < 0.05). Mineral synthesis was increased by 81% in NELL1-iPSC-MSCs at 21 d. In conclusion, NELL1 overexpression greatly enhanced the osteogenic differentiation and mineral synthesis of iPSC-MSCs on RGD-grafted CPC scaffold for the first time. The novel NELL1-iPSC-MSC seeded RGD-CPC construct is promising to enhance bone engineering.

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Section: Methodsmentioning

confidence: 99%

Effect of NELL1 gene overexpression in iPSC-MSCs seeded on calcium phosphate cement

et al. 2014

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“…Furthermore, provided that alginate itself is not capable of specific interactions with cells, [42] proteins (e.g. fibrinogen [43]), peptides or other biologically active molecules can be introduced not only to influence material stability, but also to improve alginate biocompatibility and promote interactions between hydrogel and encapsulated cells by presenting specific chemical cues.…”

Section: Discussionmentioning

confidence: 99%

Programmed cell delivery from biodegradable microcapsules for tissue repair

Draghi

Brunelli

Farè

et al. 2015

Journal of Biomaterials Science, Polymer Edition

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Injectable and resorbable hydrogels are an extremely attractive class of biomaterials. They make it possible to fill tissue defects accurately with an undoubtedly minimally invasive approach and to locally deliver cells that support repair or regeneration processes. However, their use as a cell carrier is often hindered by inadequate diffusion in bulk. A possible strategy for overcoming this transport limitation might be represented by injection of rapidly degradable cell-loaded microcapsules, so that maximum material thickness is limited by sphere radius. Here, the possibility of achieving programmable release of viable cells from alginate-based microcapsules was explored in vitro, by evaluating variations in material stability resulting from changes in hydrogel composition and assessing cell viability after encapsulation and in vitro release from microcapsules. Degradation of pure alginate microspheres was varied from a few days to several weeks by varying sodium alginate and calcium chloride concentrations. The addition of poloxamer was also found to accelerate degradation significantly, with capsule breakdown almost complete by two weeks, while chitosan was confirmed to strengthen alginate cross-linking. The presence of viable cells inside microspheres was revealed after encapsulation, and released cells were observed for all the formulations tested after a time interval dependent on bead degradation speed. These findings suggest that it may be possible to fine tune capsule breakdown by means of simple changes in material formulation and regulate, and eventually optimize, cell release for tissue repair.

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“…RGD is widely utilized in tissue engineering studies and has been used in studies with alginate [48, 49]. In the current study RGD was used a model ligand which may be replaced with more relevant cell-recognition molecules for targeting MSCs in vivo .…”

Section: Discussionmentioning

confidence: 99%

Osteogenic differentiation of human mesenchymal stem cells through alginate-graft-poly(ethylene glycol) microsphere-mediated intracellular growth factor delivery

Miao

Rao

Spees

et al. 2014

Journal of Controlled Release

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The intracellular delivery of growth factors increases opportunities for controlling cell behavior and maintaining tissue homeostasis. Recently, VEGFA was reported to enhance osteogenic differentiation of mesenchymal stem cells (MSCs) through an intracrine mechanism, suggesting a new strategy to promote bone tissue formation in osteoporotic patients. The goal of this study was to design and fabricate ligand-conjugated alginate-graft-poly(ethylene glycol) microspheres for intracellular delivery and release of VEGFA in primary human MSCs to enhance osteogenic differentiation as a potential therapeutic. Three types of microspheres were synthesized and characterized by scanning electron microscopy, in vitro drug release kinetics, MSC uptake and internalization: alginate alone (Alg), alginate-graft-poly(ethylene glycol) (Algg-PEG) and alginategraft-poly(ethylene glycol)-S-S-arginine-glycine-aspartic acid (Alg-g-RGD). Each of the different microsphere formulations successfully transported bioactive VEGFA into primary human MSCs within 48 h of culture, and significantly enhanced osteogenic differentiation compared to control treatments with empty microspheres (intracellular control) or non-encapsulated VEGFA (extracellular control). Adipogenic differentiation was not affected by the presence of VEGFA intracellularly or extracellularly. These results demonstrating the internalization of alginate-based microspheres and intracellular delivery of VEGFA support the efficacy of using this drug delivery and intracrine mechanism to control the fate of human MSCs and enhance osteogenic differentiation.

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Fast-Degradable Microbeads Encapsulating Human Umbilical Cord Stem Cells in Alginate for Muscle Tissue Engineering

Cited by 31 publications

References 71 publications

Effect of NELL1 gene overexpression in iPSC-MSCs seeded on calcium phosphate cement

Effect of NELL1 gene overexpression in iPSC-MSCs seeded on calcium phosphate cement

Programmed cell delivery from biodegradable microcapsules for tissue repair

Osteogenic differentiation of human mesenchymal stem cells through alginate-graft-poly(ethylene glycol) microsphere-mediated intracellular growth factor delivery

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