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Biomedicines
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Regenerative Medicine in Diabetes
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Regenerative Medicine in Diabetes

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Biomedical Materials and Nanomedicine".

Deadline for manuscript submissions: closed (31 July 2020) | Viewed by 18774

Special Issue Editor

Dr. Shoichiro Sumi

E-Mail Website
Guest Editor
Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Shogoin-Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan
Interests: diabetes mellitus; regenerative medicine; encapsulation; islet cell differentiation; islet xenotransplantation

Special Issue Information

Dear Colleagues,

Diabetes mellitus (DM) is caused by an insufficient function of insulin. Thus, if the definition of regenerative medicine is to cure diseases or injuries by reconstructing lost forms and/or functions, regenerative medicine for diabetes is to cure DM by reconstructing the function of insulin. As Dr. Banting stated almost a century ago in a Nobel lecture, exogenous insulin administration is not a cure for diabetes but a treatment. In that sense, transplantation of the pancreas organ or isolated islets can cure DM by reconstructing insulin action. However, current transplantation therapy for DM needs immunosuppression and human donors. Regenerative medicine can achieve similar effects without these necessities. Regenerative medicine may also prevent autoimmunity and/or islet disfunction developing DM. In this Special Issue on “Regenerative Medicine in Diabetes”, I would like to sum up our achievements and open a new vista for the future in this field. Original investigations and review articles are both welcome.

Dr. Shoichiro Sumi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • diabetes mellitus
  • regenerative medicine
  • encapsulation
  • islet cell differentiation
  • islet xenotransplantation

Published Papers (6 papers)

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Editorial

Jump to: Research, Review

3 pages, 181 KiB  
Editorial
Regenerative Medicine in Diabetes
by Shoichiro Sumi
Biomedicines 2020, 8(12), 537; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8120537 - 25 Nov 2020
Viewed by 1304
Abstract
Diabetes mellitus (DM) is caused by insufficient insulin function [...] Full article
(This article belongs to the Special Issue Regenerative Medicine in Diabetes)

Research

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14 pages, 3037 KiB  
Article
Co-Microencapsulation of Islets and MSC CellSaics, Mosaic-Like Aggregates of MSCs and Recombinant Peptide Pieces, and Therapeutic Effects of Their Subcutaneous Transplantation on Diabetes
by Yusuke Mochizuki, Ryo Kogawa, Ryuta Takegami, Kentaro Nakamura, Akira Wakabayashi, Tadashi Ito and Yasuhiro Yoshioka
Biomedicines 2020, 8(9), 318; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8090318 - 31 Aug 2020
Cited by 8 | Viewed by 2873
Abstract
The subcutaneous transplantation of microencapsulated islets has been extensively studied as a therapeutic approach for type I diabetes. However, due to the lower vascular density and strong inflammatory response in the subcutaneous area, there have been few reports of successfully normalized blood glucose [...] Read more.
The subcutaneous transplantation of microencapsulated islets has been extensively studied as a therapeutic approach for type I diabetes. However, due to the lower vascular density and strong inflammatory response in the subcutaneous area, there have been few reports of successfully normalized blood glucose levels. To address this issue, we developed mosaic-like aggregates comprised of mesenchymal stem cells (MSCs) and recombinant peptide pieces called MSC CellSaics, which provide a continuous release of angiogenic factors and anti-inflammatory cytokines. Our previous report revealed that the diabetes of immunodeficient diabetic model mice was reversed by the subcutaneous co-transplantation of the MSC CellSaics and rat islets. In this study, we focused on the development of immune-isolating microcapsules to co-encapsulate the MSC CellSaics and rat islets, and their therapeutic efficiency via subcutaneous transplantation into immunocompetent diabetic model mice. As blood glucose level was monitored for 28 days following transplantation, the normalization rate of the new immuno-isolating microcapsules was confirmed to be significantly higher than those of the microcapsules without the MSC CellSaics, and the MSC CellSaics transplanted outside the microcapsules (p < 0.01). Furthermore, the number of islets required for the treatment was reduced. In the stained sections, a larger number/area of blood vessels was observed around the new immuno-isolating microcapsules, which suggests that angiogenic factors secreted by the MSC CellSaics through the microcapsules function locally for their enhanced efficacy. Full article
(This article belongs to the Special Issue Regenerative Medicine in Diabetes)
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13 pages, 10005 KiB  
Article
A New Islet Transplantation Method Combining Mesenchymal Stem Cells with Recombinant Peptide Pieces, Microencapsulated Islets, and Mesh Bags
by Ryo Kogawa, Kentaro Nakamura and Yusuke Mochizuki
Biomedicines 2020, 8(9), 299; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8090299 - 21 Aug 2020
Cited by 20 | Viewed by 3646
Abstract
Microencapsulated islet transplantation was widely studied as a promising treatment for type 1 diabetes mellitus. However, micro-encapsulated islet transplantation has the following problems—early dysfunction of the islets due to the inflammatory reaction at the transplantation site, and hyponutrition and hypoxia due to a [...] Read more.
Microencapsulated islet transplantation was widely studied as a promising treatment for type 1 diabetes mellitus. However, micro-encapsulated islet transplantation has the following problems—early dysfunction of the islets due to the inflammatory reaction at the transplantation site, and hyponutrition and hypoxia due to a lack of blood vessels around the transplantation site, and difficulty in removal of the islets. On the other hand, we proposed a cell transplantation technique called CellSaic, which was reported to enhance the vascular induction effect of mesenchymal stem cells (MSCs) in CellSaic form, and to enhance the effect of islet transplantation through co-transplantation. Therefore, we performed islet transplantation in diabetic mice by combining three components—microencapsulated islets, MSC-CellSaic, and a mesh bag that encapsulates them and enables their removal. Mesh pockets were implanted in the peritoneal cavity of Balb/c mice as implantation sites. After 4 weeks of implantation, a pocket was opened and transplanted with (1) pancreatic islets, (2) microencapsulated islets, and (3) microencapsulated islets + MSC-CellSaic. Four weeks of observation of blood glucose levels showed that the MSC-CellSaic co-transplant group showed a marked decrease in blood glucose levels, compared to the other groups. A three-component configuration of microcapsules, MSC-CellSaic, and mesh bag was shown to enhance the efficacy of islet transplantation. Full article
(This article belongs to the Special Issue Regenerative Medicine in Diabetes)
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13 pages, 2822 KiB  
Article
Modulation of Renal Injury by Variable Expression of Myo-Inositol Oxygenase (MIOX) via Perturbation in Metabolic Sensors
by Isha Sharma, Fei Deng and Yashpal S. Kanwar
Biomedicines 2020, 8(7), 217; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8070217 - 16 Jul 2020
Cited by 3 | Viewed by 2671
Abstract
Obesity is associated with perturbations in cellular energy homeostasis and consequential renal injury leading to chronic renal disease (CKD). Myo-inositol oxygenase (MIOX), a tubular enzyme, alters redox balance and subsequent tubular injury in the settings of obesity. Mechanism(s) for such adverse changes remain [...] Read more.
Obesity is associated with perturbations in cellular energy homeostasis and consequential renal injury leading to chronic renal disease (CKD). Myo-inositol oxygenase (MIOX), a tubular enzyme, alters redox balance and subsequent tubular injury in the settings of obesity. Mechanism(s) for such adverse changes remain enigmatic. Conceivably, MIOX accentuates renal injury via reducing expression/activity of metabolic sensors, which perturb mitochondrial dynamics and, if sustained, would ultimately contribute towards CKD. In this brief communication, we utilized MIOX-TG (Transgenic) and MIOXKO mice, and subjected them to high fat diet (HFD) administration. In addition, ob/ob and ob/MIOXKO mice of comparable age were used. Mice fed with HFD had increased MIOX expression and remarkable derangements in tubular injury biomarkers. Decreased expression of p-AMPKα (phospho AMP-activated protein kinase) in the tubules was also observed, and it was accentuated in MIOX-TG mice. Interestingly, ob/ob mice also had decreased p-AMPKα expression, which was restored in ob/MIOXKO mice. Parallel changes were observed in Sirt1/Sirt3 (silent mating type information regulation 2 homolog), and expression of other metabolic sensors, i.e., PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) and Yin Yang (YY-1). In vitro experiments with tubular cells subjected to palmitate-BSA and MIOX-siRNA had results in conformity with the in vivo observations. These findings link the biology of metabolic sensors to MIOX expression in impaired cellular energy homeostasis with exacerbation/amelioration of renal injury. Full article
(This article belongs to the Special Issue Regenerative Medicine in Diabetes)
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20 pages, 22614 KiB  
Article
Bioinformatic Analyses of miRNA–mRNA Signature during hiPSC Differentiation towards Insulin-Producing Cells upon HNF4α Mutation
by Luiza Ghila, Yngvild Bjørlykke, Thomas Aga Legøy, Heidrun Vethe, Kenichiro Furuyama, Simona Chera and Helge Ræder
Biomedicines 2020, 8(7), 179; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8070179 - 27 Jun 2020
Cited by 5 | Viewed by 2474
Abstract
Mutations in the hepatocyte nuclear factor 4α (HNF4α) gene affect prenatal and postnatal pancreas development, being characterized by insulin-producing β-cell dysfunction. Little is known about the cellular and molecular mechanisms leading to β-cell failure as result of HNF4α mutation. In this study, we [...] Read more.
Mutations in the hepatocyte nuclear factor 4α (HNF4α) gene affect prenatal and postnatal pancreas development, being characterized by insulin-producing β-cell dysfunction. Little is known about the cellular and molecular mechanisms leading to β-cell failure as result of HNF4α mutation. In this study, we compared the miRNA profile of differentiating human induced pluripotent stem cells (hiPSC) derived from HNF4α+/Δ mutation carriers and their family control along the differentiation timeline. Moreover, we associated this regulation with the corresponding transcriptome profile to isolate transcript–miRNA partners deregulated in the mutated cells. This study uncovered a steep difference in the miRNA regulation pattern occurring during the posterior foregut to pancreatic endoderm transition, defining early and late differentiation regulatory windows. The pathway analysis of the miRNAome–transcriptome interactions revealed a likely gradual involvement of HNF4α+/Δ mutation in p53-mediated cell cycle arrest, with consequences for the proliferation potential, survival and cell fate acquisition of the differentiating cells. The present study is based on bioinformatics approaches and we expect that, pending further experimental validation, certain miRNAs deregulated in the HNF4α+/Δ cells would prove useful for therapy. Full article
(This article belongs to the Special Issue Regenerative Medicine in Diabetes)
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Review

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19 pages, 1293 KiB  
Review
Application of 3D Bioprinting Technologies to the Management and Treatment of Diabetic Foot Ulcers
by Chew Teng Tan, Kun Liang, Zong Heng Ngo, Christabel Thembela Dube and Chin Yan Lim
Biomedicines 2020, 8(10), 441; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines8100441 - 21 Oct 2020
Cited by 22 | Viewed by 5305
Abstract
Diabetes mellitus (DM) is a chronic metabolic disease with increasing prevalence worldwide. Diabetic foot ulcers (DFUs) are a serious complication of DM. It is estimated that 15–25% of DM patients develop DFU at least once in their lifetime. The lack of effective wound [...] Read more.
Diabetes mellitus (DM) is a chronic metabolic disease with increasing prevalence worldwide. Diabetic foot ulcers (DFUs) are a serious complication of DM. It is estimated that 15–25% of DM patients develop DFU at least once in their lifetime. The lack of effective wound dressings and targeted therapy for DFUs often results in prolonged hospitalization and amputations. As the incidence of DM is projected to rise, the demand for specialized DFU wound management will continue to increase. Hence, it is of great interest to improve and develop effective DFU-specific wound dressings and therapies. In the last decade, 3D bioprinting technology has made a great contribution to the healthcare sector, with the development of personalized prosthetics, implants, and bioengineered tissues. In this review, we discuss the challenges faced in DFU wound management and how 3D bioprinting technology can be applied to advance current treatment methods, such as biomanufacturing of composite 3D human skin substitutes for skin grafting and the development of DFU-appropriate wound dressings. Future co-development of 3D bioprinting technologies with novel treatment approaches to mitigate DFU-specific pathophysiological challenges will be key to limiting the healthcare burden associated with the increasing prevalence of DM. Full article
(This article belongs to the Special Issue Regenerative Medicine in Diabetes)
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