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Cells
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Stem Cells in Tissue Homeostasis, Regeneration and Disease
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Stem Cells in Tissue Homeostasis, Regeneration and Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: closed (20 May 2023) | Viewed by 11049

Special Issue Editor

Dr. Swarnabh Bhattacharya

E-Mail Website
Guest Editor
1. Department of Medical Oncology and Center for Functional Cancer Epigenetics, Dana–Farber Cancer Institute, Boston, MA 02215, USA
2. Departments of Medicine, Brigham & Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Interests: epithelial stem cells; organoids; tissue homeostasis; tissue plasticity; cell fate specification; epigenetics

Special Issue Information

Dear Colleagues,

Recent advances in scRNAseq, live imaging, CRISPR screening, and mathematical modeling have expanded our understanding of tissue homeostasis and its regulation by resident stem cells. Stem cells from different tissue display distinct self-renewal properties to meet tissue-specific demands. Loss of stem cells through injury, environmental factors, or genetic disease disrupts tissue homeostasis leading to pathology. Recent evidence suggests that most tissues elicit dedifferentiation of the progeny cells to cope with acute stem cell loss. However, the cellular transition states and populations driving this process remain elusive. Apart from the studies on model organisms, the advancement of directed differentiation of induced pluripotent stem cells (iPSCs) to tissue-specific cell types, in-vitro cultivation of primary human cells, and 3-D organoids hold great potential for regenerative medicine.

In this Special Issue of Cells, I invite you to contribute original research articles, reviews, or shorter perspective articles on any aspects related to the theme of Stem Cells in Tissue Homeostasis, Regeneration, and Disease. Articles describing mechanistic, functional, and cellular aspects of tissue homeostasis or disease models based on model organisms, iPSCs, primary cell culture, and 3-D organoids are highly welcome.

Dr. Swarnabh Bhattacharya
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. Cells is an international peer-reviewed open access semimonthly 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 2700 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

  • stem cells
  • cell fate
  • iPSCs
  • organoids
  • tissue plasticity
  • regenerative medicine

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (4 papers)

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Research

15 pages, 2286 KiB  
Article
TNF-α Preconditioning Improves the Therapeutic Efficacy of Mesenchymal Stem Cells in an Experimental Model of Atherosclerosis
by Aliya Sekenova, Yelena Li, Assel Issabekova, Arman Saparov and Vyacheslav Ogay
Cells 2023, 12(18), 2262; https://doi.org/10.3390/cells12182262 - 13 Sep 2023
Cited by 4 | Viewed by 1547
Abstract
Atherosclerosis (AS) is an inflammatory disease involving multiple factors in its initiation and development. In recent years, the potential application of mesenchymal stem cells (MSCs) for treating AS has been investigated. This study examined the effect of TNF-α preconditioning on MSCs’ therapeutic efficacy [...] Read more.
Atherosclerosis (AS) is an inflammatory disease involving multiple factors in its initiation and development. In recent years, the potential application of mesenchymal stem cells (MSCs) for treating AS has been investigated. This study examined the effect of TNF-α preconditioning on MSCs’ therapeutic efficacy in treating AS in ApoE KO mice. TNF-α-treated MSCs were administered to high-fat diet-treated ApoE KO mice. Cytokine and serum lipid levels were measured before and after treatment. Cryosections of the atherosclerotic aorta were stained with Oil-Red-O, and the relative areas of atherosclerotic lesions were measured. The level of Tregs were increased in TNF-α-MSC-treated animals compared to the MSCs group. In addition, the systemic administration of TNF-α-MSCs to ApoE KO mice reduced the level of proinflammatory cytokines such as TNF-α and IFN-γ and increased the level of the immunosuppressive IL-10 in the blood serum. Total cholesterol and LDL levels were decreased, and HDL levels were increased in the TNF-α-MSCs group of ApoE KO mice. A histological analysis showed that TNF-α-MSCs decreased the size of the atherosclerotic lesion in the aorta of ApoE KO mice by 38%, although there was no significant difference when compared with untreated MSCs. Thus, our data demonstrate that TNF-α-MSCs are more effective at treating AS than untreated MSCs. Full article
(This article belongs to the Special Issue Stem Cells in Tissue Homeostasis, Regeneration and Disease)
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17 pages, 4064 KiB  
Article
Human Fibroblast Growth Factor-Treated Adipose-Derived Stem Cells Facilitate Wound Healing and Revascularization in Rats with Streptozotocin-Induced Diabetes Mellitus
by So-Young Chang, Jun Hee Lee, Se Cheol Oh, Min Young Lee and Nam Kyu Lim
Cells 2023, 12(8), 1146; https://doi.org/10.3390/cells12081146 - 13 Apr 2023
Cited by 3 | Viewed by 2800
Abstract
Diabetes mellitus contributes to 15–25% of all chronic foot ulcers. Peripheral vascular disease is a cause of ischemic ulcers and exacerbates diabetic foot disease. Cell-based therapies are viable options to restore damaged vessels and induce the formation of new vessels. Adipose-derived stem cells [...] Read more.
Diabetes mellitus contributes to 15–25% of all chronic foot ulcers. Peripheral vascular disease is a cause of ischemic ulcers and exacerbates diabetic foot disease. Cell-based therapies are viable options to restore damaged vessels and induce the formation of new vessels. Adipose-derived stem cells (ADSCs) have the potential for angiogenesis and regeneration because of their greater paracrine effect. Preclinical studies are currently using other forced enhancement techniques (e.g., genetic modification or biomaterials) to increase the efficacy of human ADSC (hADSC) autotransplantation. Unlike genetic modifications and biomaterials, many growth factors have been approved by the equivalent regulatory authorities. This study confirmed the effect of enhanced human ADSC (ehADSC)s with a cocktail of FGF and other pharmacological agents to promote wound healing in diabetic foot disease. In vitro, ehADSCs exhibited a long and slender spindle-shaped morphology and showed significantly increased proliferation. In addition, it was shown that ehADSCs have more functionalities in oxidative stress toleration, stem cell stemness, and mobility. In vivo, the local transplantation of 1.2 × 106 hADSCs or ehADSCs was performed in animals with diabetes induced by STZ. The ehADSC group showed a statistically decreased wound size and increased blood flow compared with the hADSC group and the sham group. Human Nucleus Antigen (HNA) positive cells were observed in some ADSC-transplanted animals. The ehADSC group showed a relatively higher portion of HNA-positive animals than the hADSC group. The blood glucose levels showed no significant difference among the groups. In conclusion, the ehADSCs showed a better performance in vitro, compared with conventional hADSCs. Additionally, a topical injection of ehADSCs into diabetic wounds enhanced wound healing and blood flow, while improving histological markers suggesting revascularization. Full article
(This article belongs to the Special Issue Stem Cells in Tissue Homeostasis, Regeneration and Disease)
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20 pages, 7102 KiB  
Article
Modeling Blast Crisis Using Mutagenized Chronic Myeloid Leukemia-Derived Induced Pluripotent Stem Cells (iPSCs)
by Jusuf Imeri, Christophe Desterke, Paul Marcoux, Gladys Telliam, Safa Sanekli, Sylvain Barreau, Yucel Erbilgin, Theodoros Latsis, Patricia Hugues, Nathalie Sorel, Emilie Cayssials, Jean-Claude Chomel, Annelise Bennaceur-Griscelli and Ali G. Turhan
Cells 2023, 12(4), 598; https://doi.org/10.3390/cells12040598 - 12 Feb 2023
Cited by 5 | Viewed by 2472
Abstract
Purpose: To model CML progression in vitro and generate a blast crisis (BC-CML) model in vitro in order to identify new targets. Methods: Three different CML-derived iPSC lines were mutagenized with the alkylating agent ENU on a daily basis for 60 days. Cells [...] Read more.
Purpose: To model CML progression in vitro and generate a blast crisis (BC-CML) model in vitro in order to identify new targets. Methods: Three different CML-derived iPSC lines were mutagenized with the alkylating agent ENU on a daily basis for 60 days. Cells were analyzed at D12 of hematopoietic differentiation for their phenotype, clonogenicity, and transcriptomic profile. Single-cell RNA-Seq analysis has been performed at three different time points during hematopoietic differentiation in ENU-treated and untreated cells. Results: One of the CML-iPSCs, compared to its non-mutagenized counterpart, generated myeloid blasts after hematopoietic differentiation, exhibiting monoblastic patterns and expression of cMPO, CD45, CD34, CD33, and CD13. Single-cell transcriptomics revealed a delay of differentiation in the mutated condition as compared to the control with increased levels of MSX1 (mesodermal marker) and a decrease in CD45 and CD41. Bulk transcriptomics analyzed along with the GSE4170 GEO dataset reveal a significant overlap between ENU-treated cells and primary BC cells. Among overexpressed genes, CD25 was identified, and its relevance was confirmed in a cohort of CML patients. Conclusions: iPSCs are a valuable tool to model CML progression and to identify new targets. Here, we show the relevance of CD25 identified in the iPSC model as a marker of CML progression. Full article
(This article belongs to the Special Issue Stem Cells in Tissue Homeostasis, Regeneration and Disease)
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10 pages, 12376 KiB  
Communication
PAX6 Expression Patterns in the Adult Human Limbal Stem Cell Niche
by Naresh Polisetti, Günther Schlunck and Thomas Reinhard
Cells 2023, 12(3), 400; https://doi.org/10.3390/cells12030400 - 23 Jan 2023
Cited by 9 | Viewed by 3070
Abstract
Paired box 6 (PAX6), a nuclear transcription factor, determines the fate of limbal epithelial progenitor cells (LEPC) and maintains epithelial cell identity. However, the expression of PAX6 in limbal niche cells, primarily mesenchymal stromal cells (LMSC), and melanocytes is scarce and not entirely [...] Read more.
Paired box 6 (PAX6), a nuclear transcription factor, determines the fate of limbal epithelial progenitor cells (LEPC) and maintains epithelial cell identity. However, the expression of PAX6 in limbal niche cells, primarily mesenchymal stromal cells (LMSC), and melanocytes is scarce and not entirely clear. To distinctly assess the PAX6 expression in limbal niche cells, fresh and organ-cultured human corneoscleral tissues were stained immunohistochemically. Furthermore, the expression of PAX6 in cultured limbal cells was investigated. Immunostaining revealed the presence of PAX6-negative cells which were positive for vimentin and the melanocyte markers Melan-A and human melanoma black-45 in the basal layer of the limbal epithelium. PAX6 staining was not observed in the limbal stroma. Moreover, the expression of PAX6 was observed by Western blot in cultured LEPC but not in cultured LMSC or LM. These data indicate a restriction of PAX6 expression to limbal epithelial cells at the limbal stem cell niche. These observations warrant further studies for the presence of other PAX isoforms in the limbal stem cell niche. Full article
(This article belongs to the Special Issue Stem Cells in Tissue Homeostasis, Regeneration and Disease)
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