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

Bioactive Materials 2022年第9期7卷 1-14页

作者： Kihak Gwon Hye Jin Hong Alan M.Gonzalez-Suarez Michael Q.Slama daheui choi Jinkee Hong Harihara Baskaran Gulnaz Stybayeva Quinn P.Peterson Alexander Revzin Department of Physiology and Biomedical Engineering Mayo ClinicRochesterMN55902USA Department of Chemical and Biomolecular Engineering Yonsei UniversitySeoul03722Republic of Korea Department of Chemical and Biomolecular Engineering Case Western Reserve UniversityClevelandOH44106USA

Human pluripotent stem cells(hPSC)hold considerable promise as a source of adult cells for treatment of diseases ranging from diabetes to liver *** of the challenges that limit the clinical/translational impact of hPSCs are high cost and difficulty in scaling-up of existing differentiation *** 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 ***,the shell contained heparin moieties for growth factor(GF)binding and *** 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 ***,we demonstrated that one-time,1 h long loading of pluripotency signals,fibroblast growth factor(FGF)-2 and transforming growth factor(TGF)-β1,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 ***,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 ***,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.

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

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Function of hepatocyte spheroids in bioactive microcapsules is enhanced by endogenous and exogenous hepatocyte growth factor

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Bioactive Materials 2023年第10期28卷 183-195页

作者： Kihak Gwon daheui choi Jose Mde Hoyos-Vega Harihara Baskaran Alan M.Gonzalez-Suarez Seonhwa Lee Hye Jin Hong Kianna M.Nguyen Ether Dharmesh Go Sugahara Yuji Ishida Takeshi Saito Gulnaz Stybayeva Alexander Revzin Department of Physiology and Biomedical Engineering Mayo ClinicRochesterMNUSA Department of Chemical and Biomolecular Engineering Case Western Reserve UniversityClevelandOHUSA Biomedical Engineering Saint Louis UniversitySt.LouisMOUSA University of Southern Californi1 Keck School of MedicineDepartment of MedicineDivision of Gastrointestinal and Liver DiseasesLos AngelesCAUSA Research and Development Department PhoenixBioCo.LtdKagamiyam1Higashi-Hiroshim1Hiroshim1Japan USC Research Center for Liver Diseases Los AngelesCAUSA

The ability to maintain functional hepatocytes has important implications for bioartificial liver development,cell-based therapies,drug screening,and tissue *** approaches can be used to restore hepatocyte function in vitro,including coating a culture substrate with extracellular matrix(ECM),encapsulating cells within biomimetic gels(Collagen-or Matrigel-based),or co-cultivation with other *** paper describes the use of bioactive heparin-based core-shell microcapsules to form and cultivate hepatocyte *** microcapsules are comprised of an aqueous core that facilitates hepatocyte aggregation into spheroids and a heparin hydrogel shell that binds and releases growth *** demonstrate that bioactive microcapsules retain and release endogenous signals thus enhancing the function of encapsulated *** also demonstrate that hepatic function may be further enhanced by loading exogenous hepatocyte growth factor(HGF)into microcapsules and inhibiting transforming growth factor(TGF)-β1 ***,bioactive microcapsules described here represent a promising new strategy for the encapsulation and maintenance of primary hepatocytes and will be beneficial for liver tissue engineering,regenerative medicine,and drug testing applications.

关键词： Droplet microfluidics Bioactive microcapsules Hepatocyte spheroid Heparin Hepatocyte growth factor

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