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Pharmaceuticals
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New Advances in Mesenchymal Stromal Cells as Therapeutic Tools
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New Advances in Mesenchymal Stromal Cells as Therapeutic Tools

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Biopharmaceuticals".

Deadline for manuscript submissions: closed (31 May 2024) | Viewed by 31496

Special Issue Editor

Dr. Kelen Cristina Ribeiro Malmegrim

E-Mail Website
Guest Editor
School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil
Interests: immunology; hematology; cell therapy; immunotherapy; transplantation immunology; biopharmaceuticals; bioprocessing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Over the past few decades, the need for alternative treatments for various diseases has prompted scientists to focus their attention on cell-based therapies and regenerative medicine. Mesenchymal stromal cells (MSCs) may be isolated from various anatomical sites, including bone marrow, adipose tissue, and umbilical cord. These cells exhibit potent paracrine properties based on the release of different mediators, including regulatory factors, chemokines, cytokines, growth factors, and nucleic acids that can be secreted or packaged into extracellular vesicles, and are also implicated in the therapeutic effects of MSCs. The process underlying these effects likely involves the migration and homing of MSCs toward inflamed and injured tissue. During tissue healing, MSCs modulate immune responses and support tissue repair and regeneration. Advances in separation, culture, expansion, and biobanking techniques for MSCs have enabled their large-scale clinical application. This progress has been accompanied by rapid clinical utilization of MSCs in regenerative and immunomodulatory approaches to treat or prevent diseases.

The purpose of this Special Issue is to bring together contributions from specialists in cellular biology, stem cells, immunology, and bioengineering on the latest advances in understanding of the mechanisms of action underlying the therapeutic effect of MSCs, in clinical applications of MSCs for treatment of inflammatory and degenerative diseases/conditions, in developing bioengineering/priming solutions to enhance MSC effectiveness, and in establishing bioprocessing platforms for large-scale MSC production for clinical applications.

We welcome the submission of original research and review articles that cover but are not limited to the following topics:

  • Cellular and molecular mechanisms underlying therapeutic effects of MSCs;
  • Interactions between MSCs and other cell types in vitro and in vivo;
  • Bioengineering/priming solutions to boost the functions of MSCs;
  • Bioengineering strategies for improving administration of MSCs;
  • Therapeutic applications of MSCs for inflammatory and degenerative diseases;
  • Establishment of bioprocessing platforms for MSC production in a large scale for clinical applications;
  • Cellular and molecular changes induced in MSCs during the bioprocess that may compromise their therapeutic potential;
  • MSC-derived products (e.g., soluble factors and extracellular vesicles) as mediators of immunomodulation and tissue repair.

Dr. Kelen Cristina Ribeiro Malmegrim
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. Pharmaceuticals 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 2900 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

  • mesenchymal stromal cells
  • cell therapy
  • immunomodulation
  • regeneration
  • regenerative medicine
  • bioprocessing
  • bioengineering
  • inflammatory diseases
  • degenerative diseases

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Published Papers (11 papers)

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Research

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16 pages, 3366 KiB  
Article
Hydrogen Sulfide Delivery to Enhance Bone Tissue Engineering Cell Survival
by Soheila Ali Akbari Ghavimi, Trent J. Faulkner, Rama Rao Tata, August J. Hemmerla, Samantha E. Huddleston, Farnoushsadat Rezaei, Ethan S. Lungren, Rui Zhang, Erin E. Bumann and Bret D. Ulery
Pharmaceuticals 2024, 17(5), 585; https://doi.org/10.3390/ph17050585 - 2 May 2024
Viewed by 1521
Abstract
Though crucial for natural bone healing, local calcium ion (Ca2+) and phosphate ion (Pi) concentrations can exceed the cytotoxic limit leading to mitochondrial overload, oxidative stress, and cell death. For bone tissue engineering applications, H2S can be [...] Read more.
Though crucial for natural bone healing, local calcium ion (Ca2+) and phosphate ion (Pi) concentrations can exceed the cytotoxic limit leading to mitochondrial overload, oxidative stress, and cell death. For bone tissue engineering applications, H2S can be employed as a cytoprotective molecule to enhance mesenchymal stem cell (MSC) tolerance to cytotoxic Ca2+/Pi concentrations. Varied concentrations of sodium hydrogen sulfide (NaSH), a fast-releasing H2S donor, were applied to assess the influence of H2S on MSC proliferation. The results suggested a toxicity limit of 4 mM for NaSH and that 1 mM of NaSH could improve cell proliferation and differentiation in the presence of cytotoxic levels of Ca2+ (32 mM) and/or Pi (16 mM). To controllably deliver H2S over time, a novel donor molecule (thioglutamic acid—GluSH) was synthesized and evaluated for its H2S release profile. Excitingly, GluSH successfully maintained cytoprotective level of H2S over 7 days. Furthermore, MSCs exposed to cytotoxic Ca2+/Pi concentrations in the presence of GluSH were able to thrive and differentiate into osteoblasts. These findings suggest that the incorporation of a sustained H2S donor such as GluSH into CaP-based bone graft substitutes can facilitate considerable cytoprotection, making it an attractive option for complex bone regenerative engineering applications. Full article
(This article belongs to the Special Issue New Advances in Mesenchymal Stromal Cells as Therapeutic Tools)
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12 pages, 1117 KiB  
Article
Umbilical Cord Mesenchymal Stromal Cells for Steroid-Refractory Acute Graft-versus-Host Disease
by Camila Derminio Donadel, Bruno Garcia Pires, Nathália Cristine André, Thalita Cristina Mello Costa, Maristela Delgado Orellana, Sâmia Rigotto Caruso, Adriana Seber, Valéria Cortez Ginani, Alessandra Araújo Gomes, Yana Novis, George Maurício Navarro Barros, Neysimélia Costa Vilella, Gláucia Helena Martinho, Ana Karine Vieira, Andrea Tiemi Kondo, Nelson Hamerschlak, Jayr Schmidt Filho, Erick Menezes Xavier, Juliana Folloni Fernandes, Vanderson Rocha, Dimas Tadeu Covas, Rodrigo Tocantins Calado, Renato Luiz Guerino-Cunha and Gil Cunha De Santisadd Show full author list remove Hide full author list
Pharmaceuticals 2023, 16(4), 512; https://doi.org/10.3390/ph16040512 - 30 Mar 2023
Cited by 3 | Viewed by 1997
Abstract
Background: Steroid-refractory acute graft-vs.-host disease (SR-aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation with a dismal prognosis and for which there is no consensus-based second-line therapy. Ruxolitinib is not easily accessible in many countries. A possible therapy is the administration of [...] Read more.
Background: Steroid-refractory acute graft-vs.-host disease (SR-aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation with a dismal prognosis and for which there is no consensus-based second-line therapy. Ruxolitinib is not easily accessible in many countries. A possible therapy is the administration of mesenchymal stromal cells (MSCs). Methods: In this retrospective study, 52 patients with severe SR-aGVHD were treated with MSCs from umbilical cord (UC-MSCs) in nine institutions. Results: The median (range) age was 12.5 (0.3–65) years and the mean ± SD dose (×106/kg) was 4.73 ± 1.3 per infusion (median of four infusions). Overall (OR) and complete response (CR) rates on day 28 were 63.5% and 36.6%, respectively. Children (n = 35) had better OR (71.5% vs. 47.1%, p = 0.12), CR (48.6% vs. 11.8%, p = 0.03), overall survival (p = 0.0006), and relapse-free survival (p = 0.0014) than adults (n = 17). Acute adverse events (all of them mild or moderate) were detected in 32.7% of patients, with no significant difference in children and adult groups (p = 1.0). Conclusions: UC-MSCs are a feasible alternative therapy for SR-aGVHD, especially in children. The safety profile is favorable. Full article
(This article belongs to the Special Issue New Advances in Mesenchymal Stromal Cells as Therapeutic Tools)
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19 pages, 3122 KiB  
Article
Engineered Mesenchymal Stem Cells Over-Expressing BDNF Protect the Brain from Traumatic Brain Injury-Induced Neuronal Death, Neurological Deficits, and Cognitive Impairments
by Bo Young Choi, Dae Ki Hong, Beom Seok Kang, Si Hyun Lee, Seunghyuk Choi, Hyo-Jin Kim, Soon Min Lee and Sang Won Suh
Pharmaceuticals 2023, 16(3), 436; https://doi.org/10.3390/ph16030436 - 13 Mar 2023
Cited by 9 | Viewed by 2687
Abstract
Traumatic brain injury (TBI) causes transitory or permanent neurological and cognitive impairments, which can intensify over time due to secondary neuronal death. However, no therapy currently exists that can effectively treat brain injury following TBI. Here, we evaluate the therapeutic potential of irradiated [...] Read more.
Traumatic brain injury (TBI) causes transitory or permanent neurological and cognitive impairments, which can intensify over time due to secondary neuronal death. However, no therapy currently exists that can effectively treat brain injury following TBI. Here, we evaluate the therapeutic potential of irradiated engineered human mesenchymal stem cells over-expressing brain-derived neurotrophic factor (BDNF), which we denote by BDNF-eMSCs, in protecting the brain against neuronal death, neurological deficits, and cognitive impairment in TBI rats. BDNF-eMSCs were administered directly into the left lateral ventricle of the brain in rats that received TBI damage. A single administration of BDNF-eMSCs reduced TBI-induced neuronal death and glial activation in the hippocampus, while repeated administration of BDNF-eMSCs reduced not only glial activation and delayed neuronal loss but also enhanced hippocampal neurogenesis in TBI rats. In addition, BDNF-eMSCs reduced the lesion area in the damaged brain of the rats. Behaviorally, BDNF-eMSC treatment improved the neurological and cognitive functions of the TBI rats. The results presented in this study demonstrate that BDNF-eMSCs can attenuate TBI-induced brain damage through the suppression of neuronal death and increased neurogenesis, thus enhancing functional recovery after TBI, indicating the significant therapeutic potential of BDNF-eMSCs in the treatment of TBI. Full article
(This article belongs to the Special Issue New Advances in Mesenchymal Stromal Cells as Therapeutic Tools)
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13 pages, 1232 KiB  
Article
Human Mesenchymal Stem Cell (hMSC) Donor Potency Selection for the “First in Cystic Fibrosis” Phase I Clinical Trial (CEASE-CF)
by Tracey L. Bonfield, Morgan T. Sutton, David R. Fletcher, Jane Reese-Koc, Erica A. Roesch, Hillard M. Lazarus, James F. Chmiel and Arnold I. Caplan
Pharmaceuticals 2023, 16(2), 220; https://doi.org/10.3390/ph16020220 - 1 Feb 2023
Cited by 6 | Viewed by 2568
Abstract
Human Mesenchymal Stem Cell (hMSC) immunotherapy has been shown to provide both anti-inflammatory and anti-microbial effectiveness in a variety of diseases. The clinical potency of hMSCs is based upon an initial direct hMSC effect on the pro-inflammatory and anti-microbial pathophysiology as well as [...] Read more.
Human Mesenchymal Stem Cell (hMSC) immunotherapy has been shown to provide both anti-inflammatory and anti-microbial effectiveness in a variety of diseases. The clinical potency of hMSCs is based upon an initial direct hMSC effect on the pro-inflammatory and anti-microbial pathophysiology as well as sustained potency through orchestrating the host immunity to optimize the resolution of infection and tissue damage. Cystic fibrosis (CF) patients suffer from a lung disease characterized by excessive inflammation and chronic infection as well as a variety of other systemic anomalies associated with the consequences of abnormal cystic fibrosis transmembrane conductance regulator (CFTR) function. The application of hMSC immunotherapy to the CF clinical armamentarium is important even in the era of modulators when patients with an established disease still need anti-inflammatory and anti-microbial therapies. Additionally, people with CF mutations not addressed by current modulator resources need anti-inflammation and anti-infection management. Furthermore, hMSCs possess dynamic therapeutic properties, but the potency of their products is highly variable with respect to their anti-inflammatory and anti-microbial effects. Due to the variability of hMSC products, we utilized standardized in vitro and in vivo models to select hMSC donor preparations with the greatest potential for clinical efficacy. The models that were used recapitulate many of the pathophysiologic outcomes associated with CF. We applied this strategy in pursuit of identifying the optimal donor to utilize for the “First in CF” Phase I clinical trial of hMSCs as an immunotherapy and anti-microbial therapy for people with cystic fibrosis. The hMSCs screened in this study demonstrated significant diversity in antimicrobial and anti-inflammatory function using models which mimic some aspects of CF infection and inflammation. However, the variability in activity between in vitro potency and in vivo effectiveness continues to be refined. Future studies require and in-depth pursuit of hMSC molecular signatures that ultimately predict the capacity of hMSCs to function in the clinical setting. Full article
(This article belongs to the Special Issue New Advances in Mesenchymal Stromal Cells as Therapeutic Tools)
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21 pages, 2706 KiB  
Article
Differential Effects of Cytokine Versus Hypoxic Preconditioning of Human Mesenchymal Stromal Cells in Pulmonary Sepsis Induced by Antimicrobial-Resistant Klebsiella pneumoniae
by Declan Byrnes, Claire H. Masterson, Jack Brady, Senthilkumar Alagesan, Hector E. Gonzalez, Sean D. McCarthy, Juan Fandiño, Daniel P. O’Toole and John G. Laffey
Pharmaceuticals 2023, 16(2), 149; https://doi.org/10.3390/ph16020149 - 19 Jan 2023
Cited by 2 | Viewed by 3428
Abstract
Background: Pulmonary sepsis is a leading cause of hospital mortality, and sepses arising from antimicrobial-resistant (AMR) bacterial strains are particularly difficult to treat. Here we investigated the potential of mesenchymal stromal cells (MSCs) to combat established Klebsiella pneumoniae pneumosepsis and further evaluated [...] Read more.
Background: Pulmonary sepsis is a leading cause of hospital mortality, and sepses arising from antimicrobial-resistant (AMR) bacterial strains are particularly difficult to treat. Here we investigated the potential of mesenchymal stromal cells (MSCs) to combat established Klebsiella pneumoniae pneumosepsis and further evaluated MSC preconditioning and pre-activation methods. Methods: The potential for naïve and preconditioned MSCs to enhance wound healing, reduce inflammation, preserve metabolic activity, and enhance bacterial killing was assessed in vitro. Rats were subjected to intratracheal K. pneumoniae followed by the intravenous administration of MSCs. Physiological indices, blood, bronchoalveolar lavage (BAL), and tissues were obtained 72 h later. Results: In vitro assays confirmed that preconditioning enhances MSC function, accelerating pulmonary epithelial wound closure, reducing inflammation, attenuating cell death, and increasing bacterial killing. Cytomix-pre-activated MSCs are superior to naïve and hypoxia-exposed MSCs in attenuating Klebsiella pneumosepsis, improving lung compliance and oxygenation, reducing bacteria, and attenuating histologic injuries in lungs. BAL inflammatory cytokines were reduced, correlating with decreases in polymorphonuclear (PMN) cells. MSCs increased PMN apoptosis and the CD4:CD8 ratio in BAL. Systemically, granulocytes, classical monocytes, and the CD4:CD8 ratio were reduced, and nonclassical monocytes were increased. Conclusions: Preconditioning with cytokines, but not hypoxia, enhances the therapeutic potential of MSCs in clinically relevant models of K. pneumoniae-induced pneumosepsis. Full article
(This article belongs to the Special Issue New Advances in Mesenchymal Stromal Cells as Therapeutic Tools)
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14 pages, 2296 KiB  
Article
Asian Pigeonwing Plants (Clitoria ternatea) Synergized Mesenchymal Stem Cells by Modulating the Inflammatory Response in Rats with Cisplatin-Induced Acute Kidney Injury
by Fatmah A. Safhi, Salha M. ALshamrani, Areej S. Jalal, Nabil S. Awad, Hussein Sabit, Fathy Elsayed Abdelgawad, Sama S. Khalil, Dina M. Khodeer and Maysa A. Mobasher
Pharmaceuticals 2022, 15(11), 1396; https://doi.org/10.3390/ph15111396 - 13 Nov 2022
Cited by 3 | Viewed by 3140
Abstract
Acute kidney injury is a heterogeneous set of disorders distinguished by a sudden decrease in the glomerular filtration rate, which is evidenced by an increase in the serum creatinine concentration or oliguria and categorized by stage and cause. It is an ever-growing health [...] Read more.
Acute kidney injury is a heterogeneous set of disorders distinguished by a sudden decrease in the glomerular filtration rate, which is evidenced by an increase in the serum creatinine concentration or oliguria and categorized by stage and cause. It is an ever-growing health problem worldwide, with no reliable treatment. In the present study, we evaluated the role of Clitoria ternatea combined with mesenchymal stem cells in treating cisplatin-induced acute kidney injury in rats. Animals were challenged with cisplatin, followed by 400 mg/kg of Asian pigeonwing extract and/or mesenchymal stem cells (106 cells/150 g body weight). Kidney functions and enzymes were recorded, and histopathological sectioning was also performed. The expression profile of IL-1β, IL-6, and caspase-3 was assessed using the quantitative polymerase chain reaction. The obtained data indicated that mesenchymal stem cells combined with the botanical extract modulated the creatinine uric acid and urea levels. Cisplatin increased the level of malondialdehyde and decreased the levels of both superoxide dismutase and glutathione; however, the dual treatment was capable of restoring the normal levels. Furthermore, all treatments modulated the IL-6, IL-1β, and caspase-3 gene expression profiles. The obtained data shed some light on adjuvant therapy using C. ternatea and mesenchymal stem cells in treating acute kidney injury; however, further investigations are required to understand these agents’ synergistic mechanisms fully. The total RNA was extracted from the control, the positive control, and all of the therapeutically treated animals. The expression profiles of the IL-6, IL-1β, and caspase-3 genes were evaluated using the real-time polymerase chain reaction. Cisplatin treatment caused a significant upregulation in IL-6. All treatments could mitigate the IL-6-upregulating effect of cisplatin, with the mesenchymal stem cell treatment being the most effective. The same profile was observed in the IL-1β and caspase-3 genes, except that the dual treatment (mesenchymal stem cells and the botanical extract) was the most effective in ameliorating the adverse effect of cisplatin; it downregulated caspase-3 expression better than the positive control. Full article
(This article belongs to the Special Issue New Advances in Mesenchymal Stromal Cells as Therapeutic Tools)
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12 pages, 1329 KiB  
Article
Human Umbilical Cord MSC Delivered-Soluble TRAIL Inhibits the Proliferation and Promotes Apoptosis of B-ALL Cell In Vitro and In Vivo
by Fangshan Chen, Xianmei Zhong, Qian Dai, Kuo Li, Wei Zhang, Jie Wang, Yueshui Zhao, Jing Shen, Zhangang Xiao, Hongyun Xing and Jing Li
Pharmaceuticals 2022, 15(11), 1391; https://doi.org/10.3390/ph15111391 - 11 Nov 2022
Cited by 8 | Viewed by 1964
Abstract
The TNF-related apoptosis-inducing ligand (TRAIL) could induce apoptosis of leukemic cells, while showed no cytotoxic effect on normal cells. One of the limitations for application of recombinant TRAIL (rhTRAIL) in leukemia treatment is that the serum half-life of this protein is short. Gene [...] Read more.
The TNF-related apoptosis-inducing ligand (TRAIL) could induce apoptosis of leukemic cells, while showed no cytotoxic effect on normal cells. One of the limitations for application of recombinant TRAIL (rhTRAIL) in leukemia treatment is that the serum half-life of this protein is short. Gene delivery is a good strategy to prolong the half-life of TRAIL. In this study, we genetically engineered umbilical cord-MSCs to continuously express and secrete soluble TRAIL (MSC-sTRAIL), to investigate the effects of MSC-sTRAIL on B-cell acute lymphocytic leukemia (B-ALL) cells. In vitro, MSC-sTRAIL significantly inhibited the proliferation of B-ALL cells by suppressing PI3K/AKT and MEK/ERK signaling pathways, and induced apoptosis of B-ALL cells via the caspase cascade-mediated pathway and mitochondrial-mediated pathway. In vivo, MSC-sTRAIL dramatically inhibited B-ALL cell growth. Meanwhile, B-ALL-induced splenic and renal injuries were significantly alleviated after MSC-sTRAIL treatment. Moreover, the serum levels of MSC-secreted sTRAIL were still high in MSC-sTRAIL treated mice, indicating an extended half-life of sTRAIL. Our study suggests that MSC delivered-TRAIL secretion is a potential therapeutic strategy for B-ALL treatment. Full article
(This article belongs to the Special Issue New Advances in Mesenchymal Stromal Cells as Therapeutic Tools)
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20 pages, 10867 KiB  
Article
Identification of Biomarkers That Modulate Osteogenic Differentiation in Mesenchymal Stem Cells Related to Inflammation and Immunity: A Bioinformatics-Based Comprehensive Study
by Ziyi Feng, Xin Su, Ting Wang and Shu Guo
Pharmaceuticals 2022, 15(9), 1094; https://doi.org/10.3390/ph15091094 - 31 Aug 2022
Cited by 4 | Viewed by 2183
Abstract
Background: Inducing mesenchymal stem cells (MSCs) osteogenesis may be beneficial in a number of clinical applications. The aim of this study is to identify key novel biomarkers of this process and to analyze the possible regulatory effects on inflammation and immunity. Results: Seven [...] Read more.
Background: Inducing mesenchymal stem cells (MSCs) osteogenesis may be beneficial in a number of clinical applications. The aim of this study is to identify key novel biomarkers of this process and to analyze the possible regulatory effects on inflammation and immunity. Results: Seven datasets (GSE159137, GSE159138, GSE114117, GSE88865, GSE153829, GSE63754, GSE73087) were obtained from the Gene Expression Omnibus database and were assigned to either the training or the validation dataset. The least absolute shrinkage and selection operator (LASSO) logistic regression model was applied to the training data to select biomarkers of osteogenesis, which were then confirmed using the validation dataset. FK506 binding protein 5 (FKBP5), insulin-like growth factor binding protein (IGFBP2), prostaglandin E receptor 2 (PTGER2), SAM domain and HD domain-containing protein 1 (SAMHD1), and transmembrane tetratricopeptide 1 (TMTC1) were highlighted as potential biomarkers. In addition, the differential expressions of immunity and inflammation-related genes were examined and their correlations with the five identified biomarkers were analyzed. The results from performing RT-qPCR and Western blots confirmed that the levels of each of these biomarkers were all significantly increased following osteogenic differentiation of MSCs. Conclusions: Our results identify five biomarkers related to MSCs osteogenesis and allow us to identify their potential roles in immunoregulation and inflammation. Each biomarker was verified by in vitro experiments. Full article
(This article belongs to the Special Issue New Advances in Mesenchymal Stromal Cells as Therapeutic Tools)
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Review

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14 pages, 550 KiB  
Review
An Overview of Mesenchymal Stem Cell Heterogeneity and Concentration
by Elvira Maličev and Katerina Jazbec
Pharmaceuticals 2024, 17(3), 350; https://doi.org/10.3390/ph17030350 - 7 Mar 2024
Cited by 4 | Viewed by 4139
Abstract
Mesenchymal stem cells (MSCs) are of great interest in cell therapies due to the immunomodulatory and other effects they have after autologous or allogeneic transplantation. In most clinical applications, a high number of MSCs is required; therefore, the isolated MSC population must be [...] Read more.
Mesenchymal stem cells (MSCs) are of great interest in cell therapies due to the immunomodulatory and other effects they have after autologous or allogeneic transplantation. In most clinical applications, a high number of MSCs is required; therefore, the isolated MSC population must be expanded in the cell culture until the desired number is reached. Analysing freshly isolated MSCs is challenging due to their rareness and heterogeneity, which is noticeable among donors, tissues, and cell subpopulations. Although the phenotype of MSCs in tissue can differ from those of cultured cells, phenotyping and counting are usually performed only after MSC proliferation. As MSC applicability is a developing and growing field, there is a need to implement phenotyping and counting methods for freshly isolated MSCs, especially in new one-step procedures where isolated cells are implanted immediately without cell culturing. Only by analysing harvested cells can we correctly evaluate such studies. This review describes multilevel heterogeneity and concentrations of MSCs and different strategies for phenotype determination and enumeration of freshly isolated MSCs. Full article
(This article belongs to the Special Issue New Advances in Mesenchymal Stromal Cells as Therapeutic Tools)
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11 pages, 624 KiB  
Review
Mesenchymal Stem Cell Therapies Approved by Regulatory Agencies around the World
by Luis E. Fernández-Garza, Silvia A. Barrera-Barrera and Hugo A. Barrera-Saldaña
Pharmaceuticals 2023, 16(9), 1334; https://doi.org/10.3390/ph16091334 - 21 Sep 2023
Cited by 9 | Viewed by 5462
Abstract
Cellular therapy has used mesenchymal stem cells (MSCs), which in cell culture are multipotent progenitors capable of producing a variety of cells limited to the mesoderm layer. There are two types of MSC sources: (1) adult MSCs, which are obtained from bone marrow, [...] Read more.
Cellular therapy has used mesenchymal stem cells (MSCs), which in cell culture are multipotent progenitors capable of producing a variety of cells limited to the mesoderm layer. There are two types of MSC sources: (1) adult MSCs, which are obtained from bone marrow, adipose tissue, peripheral blood, and dental pulp; and (2) neonatal-tissue-derived MSCs, obtained from extra-embryonic tissues such as the placenta, amnion, and umbilical cord. Until April 2023, 1120 registered clinical trials had been using MSC therapies worldwide, but there are only 12 MSC therapies that have been approved by regulatory agencies for commercialization. Nine of the twelve MSC-approved products are from Asia, with Republic of Korea being the country with the most approved therapies. In the future, MSCs will play an important role in the treatment of many diseases. However, there are many issues to deal with before their application and usage in the medical field. Some strategies have been proposed to face these problems with the hope of reaching the objective of applying these MSC therapies at optimal therapeutic levels. Full article
(This article belongs to the Special Issue New Advances in Mesenchymal Stromal Cells as Therapeutic Tools)
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Other

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13 pages, 2642 KiB  
Study Protocol
Evaluation of Safety and Efficacy of Cell Therapy Based on Osteoblasts Derived from Umbilical Cord Mesenchymal Stem Cells for Osteonecrosis of the Femoral Head: Study Protocol for a Single-Center, Open-Label, Phase I Clinical Trial
by Seung-Hoon Baek, Bum-Jin Shim, Heejae Won, Sunray Lee, Yeon Kyung Lee, Hyun Sook Park and Shin-Yoon Kim
Pharmaceuticals 2024, 17(10), 1366; https://doi.org/10.3390/ph17101366 - 13 Oct 2024
Viewed by 670
Abstract
Although mesenchymal stem cells (MSCs) insertion has gained recent attention as a joint-preserving procedure, no study has conducted direct intralesional implantation of human umbilical cord-derived MSCs (hUCMSCs) in patients with ONFH. This is a protocol for a phase 1 clinical trial designed to [...] Read more.
Although mesenchymal stem cells (MSCs) insertion has gained recent attention as a joint-preserving procedure, no study has conducted direct intralesional implantation of human umbilical cord-derived MSCs (hUCMSCs) in patients with ONFH. This is a protocol for a phase 1 clinical trial designed to assess the safety and exploratory efficacy of human umbilical cord-derived osteoblasts (hUC-Os), osteogenic differentiation-induced cells from hUCMSCs, in patients with early-stage ONFH. Nine patients with Association Research Circulation Osseous (ARCO) stage 1 or 2 will be assigned to a low-dose (1 × 107 hUC-O cells, n = 3), medium-dose (2 × 107 cells, n = 3), and high-dose group (4 × 107 cells, n = 3) in the order of their arrival at the facility, and, depending on the occurrence of dose-limiting toxicity, up to 18 patients can be enrolled by applying the 3 + 3 escalation method. We will perform hUC-O (CF-M801) transplantation combined with core decompression and follow-up for 12 weeks according to the study protocol. Safety will be determined through adverse event assessment, laboratory tests including a panel reactive antibody test, vital sign assessment, physical examination, and electrocardiogram. Efficacy will be explored through the change in pain visual analog scale, Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index, ARCO stage, and also size and location of necrotic lesion according to Japanese Investigation Committee classification before and after the procedure. Joint preservation is important, particularly in younger, active patients with ONFH. Confirmation of the safety and efficacy of hUC-Os will lead to a further strategy to preserve joints for those suffering from ONFH and improve our current knowledge of cell therapy. Full article
(This article belongs to the Special Issue New Advances in Mesenchymal Stromal Cells as Therapeutic Tools)
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