Bioengineering in Human Induced Pluripotent Stem Cells (iPSCs)

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Regenerative Engineering".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 10939

Special Issue Editor


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Guest Editor
Principal Scientist, Umoja Biopharma, Seattle, WA, USA
Interests: bioengineering; extracellular matrix (ECM); human induced pluripotent stem cells (iPSCs); iPSC-cardiomyocytes; cancer; telomerase; epigenetics

Special Issue Information

Dear Colleagues, 

When combined with bioengineering approaches, human pluripotent stem cells hold great promise for a number of biomedical applications. Most of these applications fall into one of two general categories: cell-based modeling systems or regenerative medicine. In this Special Issue on “Bioengineering in Human Induced Pluripotent Stem Cells”, contributions tackling the many bioengineering challenges that are crucial for creating successful modeling systems and regenerative medicine approaches utilizing human-induced pluripotent stem cells (iPSCs) or human embryonic stem cells (hESCs) will be showcased.

Such modeling systems have helped further our understanding of healthy and disease states and supported improved drug testing platforms. More accurate modeling systems and high-throughput drug screening platforms have been developed by combining pluripotent stem cells with bioengineered cell culture approaches (biomimetic 3D culture systems, incorporating extracellular matrix (ECM) proteins, bioprinting, automation, etc.). These advancements, together with the ability to use human iPSCs in a patient-specific manner, have helped support a shift from personalized medicine to patient-specific therapies. However, challenges remain in the reproducibility, streamlining, and scale-up to make patient-specific therapies a viable option for most patients.

Considerable progress has been made in the field of regenerative medicine, which has focused on using iPSCs or hESCs clinically for repairing or replacing damaged cells or tissues. Key hurdles include developing scaffolds and other systems suitable for transplantation, clinical scale-up, shifting from 2D to 3D culture systems, and manufacturing demands. Most recently, the cells themselves are being bioengineered using genome editing techniques (e.g., CRISPR/Cas9) to enhance cellular performance.

Original research articles and reviews are welcome in all relevant areas of research.

Dr. Teisha J. Rowland
Guest Editor

Manuscript Submission Information

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Keywords

  • human induced pluripotent stem cells (iPSCs)
  • human embryonic stem cells (hESCs)
  • regenerative medicine
  • organoids
  • organ-on-a-chip
  • bioreactor culture systems
  • tissue bioengineering
  • biomaterials
  • biomimetic
  • extracellular matrix (ECM)
  • disease modeling
  • drug discovery
  • drug testing
  • gene editing
  • patient-specific therapies
  • clinical translation
  • transplantations

Published Papers (3 papers)

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Research

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15 pages, 3713 KiB  
Article
Microcarrier-Based Culture of Human Pluripotent Stem-Cell-Derived Retinal Pigmented Epithelium
by Mohamed A. Faynus, Jeffrey K. Bailey, Britney O. Pennington, Mika Katsura, Duncan A. Proctor, Ashley K. Yeh, Sneha Menon, Dylan G. Choi, Jane S. Lebkowski, Lincoln V. Johnson and Dennis O. Clegg
Bioengineering 2022, 9(7), 297; https://doi.org/10.3390/bioengineering9070297 - 4 Jul 2022
Cited by 3 | Viewed by 3391
Abstract
Dry age-related macular degeneration (AMD) is estimated to impact nearly 300 million individuals globally by 2040. While no treatment options are currently available, multiple clinical trials investigating retinal pigmented epithelial cells derived from human pluripotent stem cells (hPSC-RPE) as a cellular replacement therapeutic [...] Read more.
Dry age-related macular degeneration (AMD) is estimated to impact nearly 300 million individuals globally by 2040. While no treatment options are currently available, multiple clinical trials investigating retinal pigmented epithelial cells derived from human pluripotent stem cells (hPSC-RPE) as a cellular replacement therapeutic are currently underway. It has been estimated that a production capacity of >109 RPE cells annually would be required to treat the afflicted population, but current manufacturing protocols are limited, being labor-intensive and time-consuming. Microcarrier technology has enabled high-density propagation of many adherent mammalian cell types via monolayer culture on surfaces of uM-diameter matrix spheres; however, few studies have explored microcarrier-based culture of RPE cells. Here, we provide an approach to the growth, maturation, and differentiation of hPSC-RPE cells on Cytodex 1 (C1) and Cytodex 3 (C3) microcarriers. We demonstrate that hPSC-RPE cells adhere to microcarriers coated with Matrigel, vitronectin or collagen, and mature in vitro to exhibit characteristic epithelial cell morphology and pigmentation. Microcarrier-grown hPSC-RPE cells (mcRPE) are viable; metabolically active; express RPE signature genes including BEST1, RPE65, TYRP1, and PMEL17; secrete the trophic factors PEDF and VEGF; and demonstrate phagocytosis of photoreceptor outer segments. Furthermore, we show that undifferentiated hESCs also adhere to Matrigel-coated microcarriers and are amenable to directed RPE differentiation. The capacity to support hPSC-RPE cell cultures using microcarriers enables efficient large-scale production of therapeutic RPE cells sufficient to meet the treatment demands of a large AMD patient population. Full article
(This article belongs to the Special Issue Bioengineering in Human Induced Pluripotent Stem Cells (iPSCs))
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17 pages, 7084 KiB  
Article
A Biomimetic Electrospun Membrane Supports the Differentiation and Maturation of Kidney Epithelium from Human Stem Cells
by Xingrui Mou, Jessica Shah, Rohan Bhattacharya, Titilola D. Kalejaiye, Bowen Sun, Po-Chun Hsu and Samira Musah
Bioengineering 2022, 9(5), 188; https://doi.org/10.3390/bioengineering9050188 - 26 Apr 2022
Cited by 10 | Viewed by 4005
Abstract
Podocytes derived from human induced pluripotent stem (hiPS) cells are enabling studies of kidney development and disease. However, many of these studies are carried out in traditional tissue culture plates that do not accurately recapitulate the molecular and mechanical features necessary for modeling [...] Read more.
Podocytes derived from human induced pluripotent stem (hiPS) cells are enabling studies of kidney development and disease. However, many of these studies are carried out in traditional tissue culture plates that do not accurately recapitulate the molecular and mechanical features necessary for modeling tissue- and organ-level functionalities. Overcoming these limitations requires the design and application of tunable biomaterial scaffolds. Silk fibroin is an attractive biomaterial due to its biocompatibility and versatility, which include its ability to form hydrogels, sponge-like scaffolds, and electrospun fibers and membranes appropriate for tissue engineering and biomedical applications. In this study, we show that hiPS cells can be differentiated into post-mitotic kidney glomerular podocytes on electrospun silk fibroin membranes functionalized with laminin. The resulting podocytes remain viable and express high levels of podocyte-specific markers consistent with the mature cellular phenotype. The resulting podocytes were propagated for at least two weeks, enabling secondary cell-based applications and analyses. This study demonstrates for the first time that electrospun silk fibroin membrane can serve as a supportive biocompatible platform for human podocyte differentiation and propagation. We anticipate that the results of this study will pave the way for the use of electrospun membranes and other biomimetic scaffolds for kidney tissue engineering, including the development of co-culture systems and organs-on-chips microphysiological devices. Full article
(This article belongs to the Special Issue Bioengineering in Human Induced Pluripotent Stem Cells (iPSCs))
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Review

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17 pages, 341 KiB  
Review
Differentiating Human Pluripotent Stem Cells to Cardiomyocytes Using Purified Extracellular Matrix Proteins
by Ashlynn M. Barnes, Tessa B. Holmstoen, Andrew J. Bonham and Teisha J. Rowland
Bioengineering 2022, 9(12), 720; https://doi.org/10.3390/bioengineering9120720 - 22 Nov 2022
Cited by 2 | Viewed by 2858
Abstract
Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) can be differentiated into cardiomyocytes (hESC-CMs and iPSC-CMs, respectively), which hold great promise for cardiac regenerative medicine and disease modeling efforts. However, the most widely employed differentiation protocols require undefined substrates that [...] Read more.
Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) can be differentiated into cardiomyocytes (hESC-CMs and iPSC-CMs, respectively), which hold great promise for cardiac regenerative medicine and disease modeling efforts. However, the most widely employed differentiation protocols require undefined substrates that are derived from xenogeneic (animal) products, contaminating resultant hESC- and iPSC-CM cultures with xenogeneic proteins and limiting their clinical applicability. Additionally, typical hESC- and iPSC-CM protocols produce CMs that are significantly contaminated by non-CMs and that are immature, requiring lengthy maturation procedures. In this review, we will summarize recent studies that have investigated the ability of purified extracellular matrix (ECM) proteins to support hESC- and iPSC-CM differentiation, with a focus on commercially available ECM proteins and coatings to make such protocols widely available to researchers. The most promising of the substrates reviewed here include laminin-521 with laminin-221 together or Synthemax (a synthetic vitronectin-based peptide coating), which both resulted in highly pure CM cultures. Future efforts are needed to determine whether combinations of specific purified ECM proteins or derived peptides could further improve CM maturation and culture times, and significantly improve hESC- and iPSC-CM differentiation protocols. Full article
(This article belongs to the Special Issue Bioengineering in Human Induced Pluripotent Stem Cells (iPSCs))
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