4.8 Article

Bioactive hydrogel microcapsules for guiding stem cell fate decisions by release and reloading of growth factors

期刊

BIOACTIVE MATERIALS
卷 15, 期 -, 页码 1-14

出版社

KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.12.008

关键词

Droplet microfluidics; Bioactive core-shell microcapsule; Growth factor release; 3D stem cell culture; Stem cell differentiation

资金

  1. Mayo Clinic Center for Regenerative Medicine
  2. J.W. Kieckhefer Foundation
  3. Al Nahyan Foundation, from Regenerative Medicine Minnesota [RMM 101617 TR 004]
  4. NIH [DK107255, EB021911]

向作者/读者索取更多资源

In this study, bioactive microcapsules were developed to address the challenges of high cost and difficulty in scaling-up of human pluripotent stem cells (hPSC) differentiation protocols. The results showed that these microcapsules were able to induce and maintain pluripotency of hPSCs, as well as improve the differentiation outcomes.
Human pluripotent stem cells (hPSC) hold considerable promise as a source of adult cells for treatment of diseases ranging from diabetes to liver failure. Some of the challenges that limit the clinical/translational impact of hPSCs are high cost and difficulty in scaling-up of existing differentiation protocols. In this paper, we sought to address these challenges through the development of bioactive microcapsules. A co-axial flow focusing microfluidic device was used to encapsulate hPSCs in microcapsules comprised of an aqueous core and a hydrogel shell. Importantly, the shell contained heparin moieties for growth factor (GF) binding and release. The aqueous core enabled rapid aggregation of hPSCs into 3D spheroids while the bioactive hydrogel shell was used to load inductive cues driving pluripotency maintenance and endodermal differentiation. Specifically, we demonstrated that one-time, 1 h long loading of pluripotency signals, fibroblast growth factor (FGF)-2 and transforming growth factor (TGF)-beta 1, into bioactive microcapsules was sufficient to induce and maintain pluripotency of hPSCs over the course of 5 days at levels similar to or better than a standard protocol with soluble GFs. Furthermore, stem cell-carrying microcapsules that previously contained pluripotency signals could be reloaded with an endodermal cue, Nodal, resulting in higher levels of endodermal markers compared to stem cells differentiated in a standard protocol. Overall, bioactive heparin-containing core-shell microcapsules decreased GF usage five-fold while improving stem cell phenotype and are well suited for 3D cultivation of hPSCs.

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