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Stem Cells—from Bench to Bedside 2021

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 43944

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Guest Editor
Department of Transplantation, Jagiellonian University, Krakow, Poland
Interests: cervical cancer; metabolic reprogramming; metformin; caffeic acid; 5′-adenosine monophosphate-activated protein kinase (AMPK)
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Special Issue Information

Dear Colleagues,

Despite enormous progress in cardiovascular medicine, many fundamental treatments remain palliative rather than curative, leading to suboptimal clinical outcomes. One such example is heart failure, resulting from loss of contractile myocardial tissue.

The emergence of a new field, regenerative medicine with cell replacement therapy enabling recovery of injured tissues and activation of endogenous processes of tissue repair, opens novel paths and new perspectives for development of curative therapies. In this Special Issue devoted to stem cell-based therapies we will discuss recent breakthroughs both in the areas of basic and translational research and clinical medicine. We aim to depict cutting-edge data on recent progress in understanding stem cells biology in relation to their therapeutic potential, new approaches in tracking and imaging of both stem cells and tissues/organs undergoing regeneration, and data from clinical trials of cell-based therapies. Moreover, the mechanisms of stem cells activity including extracellular vesicle production and potential use will be presented.

Prof. Dr. Marcin Majka
Guest Editor

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Keywords

  • stem cells
  • cell tracking
  • tissue imaging
  • replacement therapy
  • extracellular vesicles

Published Papers (13 papers)

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Research

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17 pages, 3725 KiB  
Article
Adipose-Derived Stem Cells Preincubated with Green Tea EGCG Enhance Pancreatic Tissue Regeneration in Rats with Type 1 Diabetes through ROS/Sirt1 Signaling Regulation
by Tung-Sheng Chen, Wei-Yu Liao, Chi-Wen Huang and Chin-Hsien Chang
Int. J. Mol. Sci. 2022, 23(6), 3165; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063165 - 15 Mar 2022
Cited by 8 | Viewed by 2665
Abstract
Type 1 diabetes stem-cell-based therapy is one of the best therapeutic approaches for pancreatic damage treatment due to stem cell tissue regeneration. Epigallocatechin gallate (EGCG) is one of the active components found in green tea. Experimental results suggest that EGCG shows beneficial effects [...] Read more.
Type 1 diabetes stem-cell-based therapy is one of the best therapeutic approaches for pancreatic damage treatment due to stem cell tissue regeneration. Epigallocatechin gallate (EGCG) is one of the active components found in green tea. Experimental results suggest that EGCG shows beneficial effects on cell protection. This study explores whether a better pancreatic regeneration therapeutic effect could be found in mesenchymal stem cells pretreated with EGCG compared to stem cells without EGCG pretreatment. A cell model confirmed that adipose-derived stem cells (ADSC) incubated with EGCG increase cell viability under high-glucose (HG) stress. This is due to survival marker p-Akt expression. In an animal model, type 1 diabetes induced the activation of several pathological signals, including islet size reduction, extracellular fibrotic collagen deposition, oxidative stress elevation, survival pathway suppression, apoptosis signaling induction, and Sirt1 antioxidant pathway downregulation. Ordinary ADSC transplantation slightly improved the above pathological signals. Further, EGCG-pretreated ADSC transplantation significantly improved the above pathological conditions. Taken together, EGCG-pretreated ADSCs show clinical potential in the treatment of patients with type 1 diabetes through the regeneration of damaged pancreatic tissues. Full article
(This article belongs to the Special Issue Stem Cells—from Bench to Bedside 2021)
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17 pages, 21791 KiB  
Article
Role of Nuclear-Receptor-Related 1 in the Synergistic Neuroprotective Effect of Umbilical Cord Blood and Erythropoietin Combination Therapy in Hypoxic Ischemic Encephalopathy
by Joo-Wan Choi, Su Jung Kang, Jee In Choi, KyuBum Kwack and MinYoung Kim
Int. J. Mol. Sci. 2022, 23(5), 2900; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052900 - 07 Mar 2022
Cited by 3 | Viewed by 2259
Abstract
Neonatal hypoxic–ischemic encephalopathy (HIE) results in neurological impairments; cell-based therapy has been suggested as a therapeutic avenue. Previous research has demonstrated the synergistically potentiated therapeutic efficacy of human umbilical cord blood (UCB) by combining recombinant human erythropoietin (EPO) treatment for recovery from HIE. [...] Read more.
Neonatal hypoxic–ischemic encephalopathy (HIE) results in neurological impairments; cell-based therapy has been suggested as a therapeutic avenue. Previous research has demonstrated the synergistically potentiated therapeutic efficacy of human umbilical cord blood (UCB) by combining recombinant human erythropoietin (EPO) treatment for recovery from HIE. However, its molecular mechanism is not entirely understood. In the present study, we analyzed the mechanisms underlying the effect of combination treatment with EPO and UCB by transcriptomic analysis, followed by gene enrichment analysis. Mouse HIE model of the neonate was prepared and randomly divided into five groups: sham, HIE, and UCB, EPO, and UCB+EPO treatments after HIE. A total of 376 genes were differentially expressed when |log2FC| ≥ 1-fold change expression values were considered to be differentially expressed between UCB+EPO and HIE. Further assessment through qRT-PCR and gene enrichment analysis confirmed the expression and correlation of its potential target, Nurr1, as an essential gene involved in the synergistic effect of the UCB+EPO combination. The results indicated the remarkable activation of Wnt/β-catenin signaling by reducing the infarct size by UCB+EPO treatment, accompanied by Nurr1 activity. In conclusion, these findings suggest that the regulation of Nurr1 through the Wnt/β-catenin pathway exerts a synergistic neuroprotective effect in UCB and EPO combination treatment. Full article
(This article belongs to the Special Issue Stem Cells—from Bench to Bedside 2021)
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17 pages, 4617 KiB  
Article
Highly Effective Protocol for Differentiation of Induced Pluripotent Stem Cells (iPS) into Melanin-Producing Cells
by Maciej Sułkowski, Marta Kot, Bogna Badyra, Anna Paluszkiewicz, Przemysław M. Płonka, Michał Sarna, Dominika Michalczyk-Wetula, Fabio A. Zucca, Luigi Zecca and Marcin Majka
Int. J. Mol. Sci. 2021, 22(23), 12787; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222312787 - 26 Nov 2021
Cited by 2 | Viewed by 2603
Abstract
Melanin is a black/brown pigment present in abundance in human skin. Its main function is photo-protection of underlying tissues from harmful UV light. Natural sources of isolated human melanin are limited; thus, in vitro cultures of human cells may be a promising source [...] Read more.
Melanin is a black/brown pigment present in abundance in human skin. Its main function is photo-protection of underlying tissues from harmful UV light. Natural sources of isolated human melanin are limited; thus, in vitro cultures of human cells may be a promising source of human melanin. Here, we present an innovative in vitro differentiation protocol of induced pluripotent stem cells (iPS) into melanin-producing cells, delivering highly pigmented cells in quantity and quality incomparably higher than any other methods previously described. Pigmented cells constitute over 90% of a terminally differentiated population and exhibit features characteristic for melanocytes, i.e., expression of specific markers such as MITF-M (microphthalmia-associated transcription factor isoform M), TRP-1 (tyrosinase-related protein 1), and TYR (tyrosinase) and accumulation of black pigment in organelles closely resembling melanosomes. Black pigment is unambiguously identified as melanin with features corresponding to those of melanin produced by typical melanocytes. The advantage of our method is that it does not require any sophisticated procedures and can be conducted in standard laboratory conditions. Moreover, our protocol is highly reproducible and optimized to generate high-purity melanin-producing cells from iPS cells; thus, it can serve as an unlimited source of human melanin for modeling human skin diseases. We speculate that FGF-8 might play an important role during differentiation processes toward pigmented cells. Full article
(This article belongs to the Special Issue Stem Cells—from Bench to Bedside 2021)
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13 pages, 3285 KiB  
Article
S100A8/A9 Enhances Immunomodulatory and Tissue-Repairing Properties of Human Amniotic Mesenchymal Stem Cells in Myocardial Ischemia-Reperfusion Injury
by Tzu-Jou Chen, Yen-Ting Yeh, Fu-Shiang Peng, Ai-Hsien Li and Shinn-Chih Wu
Int. J. Mol. Sci. 2021, 22(20), 11175; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222011175 - 16 Oct 2021
Cited by 9 | Viewed by 2343
Abstract
Paracrine factors of human mesenchymal stem cells (hMSCs) have the potential of preventing adverse cardiac remodeling after myocardial infarction (MI). S100A8 and S100A9 are calcium-binding proteins playing essential roles in the regulation of inflammation and fibrous tissue formation, and they might modulate the [...] Read more.
Paracrine factors of human mesenchymal stem cells (hMSCs) have the potential of preventing adverse cardiac remodeling after myocardial infarction (MI). S100A8 and S100A9 are calcium-binding proteins playing essential roles in the regulation of inflammation and fibrous tissue formation, and they might modulate the paracrine effect of hMSCs. We isolated human amniotic mesenchymal stem cells (hAMSCs) and examined the changes in the expression level of regulatory genes of inflammation and fibrosis after hAMSCs were treated with S100A8/A9. The anti-inflammatory and anti-fibrotic effects of hAMSCs pretreated with S100A8/A9 were shown to be superior to those of hAMSCs without S100A8/A9 pretreatment in the cardiomyocyte hypoxia/reoxygenation experiment. We established a murine myocardial ischemia/reperfusion model to compare the therapeutic effects of the conditioned medium of hAMSCs with or without S100A8/A9 pretreatment. We found the hearts administered with a conditioned medium of hAMSCs with S100A8/A9 pretreatment had better left ventricular systolic function on day 7, 14, and 28 after MI. These results suggest S100A8/A9 enhances the paracrine therapeutic effects of hAMSCs in aspects of anti-inflammation, anti-fibrosis, and cardiac function preservation after MI. Full article
(This article belongs to the Special Issue Stem Cells—from Bench to Bedside 2021)
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15 pages, 8676 KiB  
Article
Serum-Derived Neuronal Exosomal miRNAs as Biomarkers of Acute Severe Stress
by Minkyoung Sung, Soo-Eun Sung, Kyung-Ku Kang, Joo-Hee Choi, Sijoon Lee, KilSoo Kim, Ju-Hyeon Lim, Gun Woo Lee, Hyo-Deog Rim, Byung-Soo Kim, Seunghee Won, Kyungmin Kim, Seoyoung Jang, Min-Soo Seo and Jungmin Woo
Int. J. Mol. Sci. 2021, 22(18), 9960; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22189960 - 15 Sep 2021
Cited by 5 | Viewed by 2377
Abstract
Stress is the physical and psychological tension felt by an individual while adapting to difficult situations. Stress is known to alter the expression of stress hormones and cause neuroinflammation in the brain. In this study, miRNAs in serum-derived neuronal exosomes (nEVs) were analyzed [...] Read more.
Stress is the physical and psychological tension felt by an individual while adapting to difficult situations. Stress is known to alter the expression of stress hormones and cause neuroinflammation in the brain. In this study, miRNAs in serum-derived neuronal exosomes (nEVs) were analyzed to determine whether differentially expressed miRNAs could be used as biomarkers of acute stress. Specifically, acute severe stress was induced in Sprague-Dawley rats via electric foot-shock treatment. In this acute severe-stress model, time-dependent changes in the expression levels of stress hormones and neuroinflammation-related markers were analyzed. In addition, nEVs were isolated from the serum of control mice and stressed mice at various time points to determine when brain damage was most prominent; this was found to be 7 days after foot shock. Next-generation sequencing was performed to compare neuronal exosomal miRNA at day 7 with the neuronal exosomal miRNA of the control group. From this analysis, 13 upregulated and 11 downregulated miRNAs were detected. These results show that specific miRNAs are differentially expressed in nEVs from an acute severe-stress animal model. Thus, this study provides novel insights into potential stress-related biomarkers. Full article
(This article belongs to the Special Issue Stem Cells—from Bench to Bedside 2021)
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13 pages, 2445 KiB  
Article
Effects of Normal Synovial Fluid and Interferon Gamma on Chondrogenic Capability and Immunomodulatory Potential Respectively on Equine Mesenchymal Stem Cells
by Mohammed Zayed, Steve Adair and Madhu Dhar
Int. J. Mol. Sci. 2021, 22(12), 6391; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126391 - 15 Jun 2021
Cited by 7 | Viewed by 2116
Abstract
Synovial fluid contains cytokines, growth factors and resident mesenchymal stem cells (MSCs). The present study aimed to (1) determine the effects of autologous and allogeneic synovial fluid on viability, proliferation and chondrogenesis of equine bone marrow MSCs (BMMSCs) and (2) compare the immunomodulatory [...] Read more.
Synovial fluid contains cytokines, growth factors and resident mesenchymal stem cells (MSCs). The present study aimed to (1) determine the effects of autologous and allogeneic synovial fluid on viability, proliferation and chondrogenesis of equine bone marrow MSCs (BMMSCs) and (2) compare the immunomodulatory properties of equine synovial fluid MSCs (SFMSCs) and BMMSCs after stimulation with interferon gamma (INF-γ). To meet the first aim of the study, the proliferation and viability of MSCs were evaluated by MTS and calcein AM staining assays. To induce chondrogenesis, MSCs were cultured in a medium containing TGF-β1 or different concentrations of synovial fluid. To meet the second aim, SFMSCs and BMMSCs were stimulated with IFN-γ. The concentration of indoleamine-2,3-dioxygenase (IDO) and nitric oxide (NO) were examined. Our results show that MSCs cultured in autologous or allogeneic synovial fluid could maintain proliferation and viability activities. Synovial fluid affected chondrocyte differentiation significantly, as indicated by increased glycosaminoglycan contents, compared to the chondrogenic medium containing 5 ng/mL TGF-β1. After culturing with IFN-γ, the conditioned media of both BMMSCs and SFMSCs showed increased concentrations of IDO, but not NO. Stimulating MSCs with synovial fluid or IFN-γ could enhance chondrogenesis and anti-inflammatory activity, respectively, suggesting that the joint environment is suitable for chondrogenesis. Full article
(This article belongs to the Special Issue Stem Cells—from Bench to Bedside 2021)
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11 pages, 1011 KiB  
Article
Localization and Maintenance of Engrafted Mesenchymal Stem Cells Administered via Renal Artery in Kidneys with Ischemia-Reperfusion Injury
by Yumi Yamada, Ayumu Nakashima, Shigehiro Doi, Naoki Ishiuchi, Ryo Kanai, Kisho Miyasako and Takao Masaki
Int. J. Mol. Sci. 2021, 22(8), 4178; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084178 - 17 Apr 2021
Cited by 5 | Viewed by 2867
Abstract
Mesenchymal stem cells (MSCs) are a potential therapeutic tool for preventing the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). Herein, we investigated the localization and maintenance of engrafted human bone marrow-derived MSCs in rats subjected to a renal ischemia-reperfusion [...] Read more.
Mesenchymal stem cells (MSCs) are a potential therapeutic tool for preventing the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). Herein, we investigated the localization and maintenance of engrafted human bone marrow-derived MSCs in rats subjected to a renal ischemia-reperfusion injury (IRI) and compared the effectiveness of two intravascular injection routes via the renal artery or inferior vena cava. Renal artery injection of MSCs was more effective than intravenous injection at reducing IRI-induced renal fibrosis. Additionally, MSCs injected through the renal artery persisted in injured kidneys for over 21 days, whereas MSCs injected through the inferior vena cava survived for less than 7 days. This difference may be attributed to the antifibrotic effects of MSCs. Interestingly, MSCs injected through the renal artery were localized primarily in glomeruli until day 3 post-IRI, and they decreased in number thereafter. In contrast, the number of MSCs localized in tubular walls, and the interstitium increased gradually until day 21 post-IRI. This localization change may be related to areas of damage caused by IRI because ischemia-induced AKI leads to tubular cell damage. Taken together, these findings suggest renal artery injection of MSCs may be useful for preventing the progression of AKI to CKD. Full article
(This article belongs to the Special Issue Stem Cells—from Bench to Bedside 2021)
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Review

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21 pages, 1878 KiB  
Review
A Review of Prostate Organogenesis and a Role for iPSC-Derived Prostate Organoids to Study Prostate Development and Disease
by Adriana Buskin, Parmveer Singh, Oliver Lorenz, Craig Robson, Douglas W. Strand and Rakesh Heer
Int. J. Mol. Sci. 2021, 22(23), 13097; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222313097 - 03 Dec 2021
Cited by 5 | Viewed by 3246
Abstract
The prostate is vulnerable to two major age-associated diseases, cancer and benign enlargement, which account for significant morbidity and mortality for men across the globe. Prostate cancer is the most common cancer reported in men, with over 1.2 million new cases diagnosed and [...] Read more.
The prostate is vulnerable to two major age-associated diseases, cancer and benign enlargement, which account for significant morbidity and mortality for men across the globe. Prostate cancer is the most common cancer reported in men, with over 1.2 million new cases diagnosed and 350,000 deaths recorded annually worldwide. Benign prostatic hyperplasia (BPH), characterised by the continuous enlargement of the adult prostate, symptomatically afflicts around 50% of men worldwide. A better understanding of the biological processes underpinning these diseases is needed to generate new treatment approaches. Developmental studies of the prostate have shed some light on the processes essential for prostate organogenesis, with many of these up- or downregulated genes expressions also observed in prostate cancer and/or BPH progression. These insights into human disease have been inferred through comparative biological studies relying primarily on rodent models. However, directly observing mechanisms of human prostate development has been more challenging due to limitations in accessing human foetal material. Induced pluripotent stem cells (iPSCs) could provide a suitable alternative as they can mimic embryonic cells, and iPSC-derived prostate organoids present a significant opportunity to study early human prostate developmental processes. In this review, we discuss the current understanding of prostate development and its relevance to prostate-associated diseases. Additionally, we detail the potential of iPSC-derived prostate organoids for studying human prostate development and disease. Full article
(This article belongs to the Special Issue Stem Cells—from Bench to Bedside 2021)
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11 pages, 704 KiB  
Review
Role of Stem Cells in the Ovarian Tissue Cryopreservation and Transplantation for Fertility Preservation
by Jeong Min Kim, Seongmin Kim and Sanghoon Lee
Int. J. Mol. Sci. 2021, 22(22), 12482; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212482 - 19 Nov 2021
Cited by 3 | Viewed by 2394
Abstract
Although the cancer survival rate has increased, cancer treatments, including chemotherapy and radiotherapy, can cause ovarian failure and infertility in women of reproductive age. Preserving fertility throughout cancer treatment is critical for maintaining quality of life. Fertility experts should propose individualized fertility preservation [...] Read more.
Although the cancer survival rate has increased, cancer treatments, including chemotherapy and radiotherapy, can cause ovarian failure and infertility in women of reproductive age. Preserving fertility throughout cancer treatment is critical for maintaining quality of life. Fertility experts should propose individualized fertility preservation methods based on the patient’s marital status, pubertal status, partner status, and the urgency of treatment. Widely practiced fertility preservation methods, including ovarian transposition and embryo and oocyte cryopreservation, are inappropriate for prepubertal girls or those needing urgent initiation of cancer treatment. Ovarian tissue cryopreservation and transplantation, an emerging new technology, may be a solution for these cancer patients. The use of stem cells in ovarian tissue cryopreservation and transplantation increases oxygenation, angiogenesis, and follicle survival rates. This review discusses the recent advances in ovarian tissue cryopreservation and transplantation with special focus on the use of stem cells to improve fertilization techniques. Full article
(This article belongs to the Special Issue Stem Cells—from Bench to Bedside 2021)
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15 pages, 802 KiB  
Review
Hypoparathyroidism: State of the Art on Cell and Tissue Therapies
by Francesca Miglietta, Gaia Palmini, Francesca Giusti, Simone Donati, Cinzia Aurilia, Teresa Iantomasi and Maria Luisa Brandi
Int. J. Mol. Sci. 2021, 22(19), 10272; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910272 - 24 Sep 2021
Cited by 6 | Viewed by 5546
Abstract
Hypoparathyroidism is an endocrine disorder characterized by low serum calcium levels, high serum phosphorus levels, and by inappropriate or absent secretion of the parathyroid hormone (PTH). The most common therapeutic strategy to treat this condition is hormone replacement therapy with calcium and vitamin [...] Read more.
Hypoparathyroidism is an endocrine disorder characterized by low serum calcium levels, high serum phosphorus levels, and by inappropriate or absent secretion of the parathyroid hormone (PTH). The most common therapeutic strategy to treat this condition is hormone replacement therapy with calcium and vitamin D but, unfortunately, in the long term this treatment may not be sufficient to compensate for the loss of endocrine function. Glandular autotransplantation is considered the most effective technique in place of replacement therapy. Although it leads to excellent results in most cases, autotransplantation is not always possible. Allograft is a good way to treat patients who have not been able to undergo autograft, but this technique has limited success due to side effects related to tissue rejection. This therapy is supported by systemic immunosuppression, which leads to the onset of serious side effects in patients, with a risk of endocrine toxicity. Today, research on endocrine disorders is focused on discovering alternative graft therapies that can allow optimal results with the fewest possible side effects. In this review, we will make an update on the current state of the art about the cell and tissue therapy as treatment for hypoparathyroidism, to identify which type of therapeutic strategy could be valid for a future clinical use. Full article
(This article belongs to the Special Issue Stem Cells—from Bench to Bedside 2021)
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25 pages, 665 KiB  
Review
Cellular Therapy for the Treatment of Paediatric Respiratory Disease
by Laura C. Brennan, Andrew O’Sullivan and Ronan MacLoughlin
Int. J. Mol. Sci. 2021, 22(16), 8906; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168906 - 18 Aug 2021
Cited by 12 | Viewed by 2996
Abstract
Respiratory disease is the leading cause of death in children under the age of 5 years old. Currently available treatments for paediatric respiratory diseases including bronchopulmonary dysplasia, asthma, cystic fibrosis and interstitial lung disease may ameliorate symptoms but do not offer a cure. [...] Read more.
Respiratory disease is the leading cause of death in children under the age of 5 years old. Currently available treatments for paediatric respiratory diseases including bronchopulmonary dysplasia, asthma, cystic fibrosis and interstitial lung disease may ameliorate symptoms but do not offer a cure. Cellular therapy may offer a potential cure for these diseases, preventing disease progression into adulthood. Induced pluripotent stem cells, mesenchymal stromal cells and their secretome have shown great potential in preclinical models of lung disease, targeting the major pathological features of the disease. Current research and clinical trials are focused on the adult population. For cellular therapies to progress from preclinical studies to use in the clinic, optimal cell type dosage and delivery methods need to be established and confirmed. Direct delivery of these therapies to the lung as aerosols would allow for lower doses with a higher target efficiency whilst avoiding potential effect of systemic delivery. There is a clear need for research to progress into the clinic for the treatment of paediatric respiratory disease. Whilst research in the adult population forms a basis for the paediatric population, varying disease pathology and anatomical differences in paediatric patients means a paediatric-centric approach must be taken. Full article
(This article belongs to the Special Issue Stem Cells—from Bench to Bedside 2021)
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27 pages, 443 KiB  
Review
Cell and Gene Therapy for Anemia: Hematopoietic Stem Cells and Gene Editing
by Dito Anurogo, Nova Yuli Prasetyo Budi, Mai-Huong Thi Ngo, Yen-Hua Huang and Jeanne Adiwinata Pawitan
Int. J. Mol. Sci. 2021, 22(12), 6275; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126275 - 10 Jun 2021
Cited by 15 | Viewed by 7317
Abstract
Hereditary anemia has various manifestations, such as sickle cell disease (SCD), Fanconi anemia, glucose-6-phosphate dehydrogenase deficiency (G6PDD), and thalassemia. The available management strategies for these disorders are still unsatisfactory and do not eliminate the main causes. As genetic aberrations are the main causes [...] Read more.
Hereditary anemia has various manifestations, such as sickle cell disease (SCD), Fanconi anemia, glucose-6-phosphate dehydrogenase deficiency (G6PDD), and thalassemia. The available management strategies for these disorders are still unsatisfactory and do not eliminate the main causes. As genetic aberrations are the main causes of all forms of hereditary anemia, the optimal approach involves repairing the defective gene, possibly through the transplantation of normal hematopoietic stem cells (HSCs) from a normal matching donor or through gene therapy approaches (either in vivo or ex vivo) to correct the patient’s HSCs. To clearly illustrate the importance of cell and gene therapy in hereditary anemia, this paper provides a review of the genetic aberration, epidemiology, clinical features, current management, and cell and gene therapy endeavors related to SCD, thalassemia, Fanconi anemia, and G6PDD. Moreover, we expound the future research direction of HSC derivation from induced pluripotent stem cells (iPSCs), strategies to edit HSCs, gene therapy risk mitigation, and their clinical perspectives. In conclusion, gene-corrected hematopoietic stem cell transplantation has promising outcomes for SCD, Fanconi anemia, and thalassemia, and it may overcome the limitation of the source of allogenic bone marrow transplantation. Full article
(This article belongs to the Special Issue Stem Cells—from Bench to Bedside 2021)

Other

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11 pages, 1043 KiB  
Case Report
Efficacy of Cord Blood Cell Therapy for Hutchinson–Gilford Progeria Syndrome—A Case Report
by Mi Ri Suh, Ikhyun Lim, Jongwook Kim, Pil-Sung Yang, Jin Seung Choung, Hye Ryeong Sim, Sung Chan Ha and MinYoung Kim
Int. J. Mol. Sci. 2021, 22(22), 12316; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212316 - 15 Nov 2021
Cited by 3 | Viewed by 3312
Abstract
Hutchinson–Gilford progeria syndrome (HGPS) is an extremely rare premature aging disorder characterized by short stature and atherosclerosis-induced death within teenage years. A 13-year-old male diagnosed with HGPS was administered three intravenous infusions of allogeneic cord blood (CB) cells from unrelated donors at four-month [...] Read more.
Hutchinson–Gilford progeria syndrome (HGPS) is an extremely rare premature aging disorder characterized by short stature and atherosclerosis-induced death within teenage years. A 13-year-old male diagnosed with HGPS was administered three intravenous infusions of allogeneic cord blood (CB) cells from unrelated donors at four-month intervals to evaluate the safety and its therapeutic efficacy. Adverse events were monitored in addition to height, weight, laboratory blood tests, joint range of motion (ROM), and carotid Doppler. Cytokine and receptor assays were also performed. The patient exhibited an increase in growth rate for both height and weight. One year after therapy initiation, evident amelioration in pulse wave velocity, bilateral maximal intima-media thickness, and dyslipidemic status were observed, which were in abrupt aggravation prior to treatment. Further, an increase in flexibility occurred in some joints of the upper extremities. No serious adverse events were observed throughout the study period and one year beyond. A molecular assay revealed downregulation of proinflammatory and atherosclerosis, representing cytokine expressions following the administration of CB cells. This is the first reported case of an allogeneic CB trial in a patient with HGPS showing therapeutic effects of CB with improvements in anthropometric measures, joint ROM with amelioration of atherosclerosis, and dyslipidemia induced by anti-inflammatory and anti-atherosclerotic responses. Full article
(This article belongs to the Special Issue Stem Cells—from Bench to Bedside 2021)
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