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Cells
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Stem Cell Therapy for Autoimmune Diseases
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Stem Cell Therapy for Autoimmune Diseases

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

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 30563

Special Issue Editors

Dr. Györgyi Műzes

E-Mail Website
Guest Editor
Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
Interests: inflammation; cancer; autophagy; carcinogenesis; innate immunity; autoimmune diseases; stem cells
Special Issues, Collections and Topics in MDPI journals
Dr. Ferenc Sipos

E-Mail Website
Guest Editor
Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
Interests: innate immunity; TLR9-signaling; autophagy; inflammation and cancer; inflammatory bowel disease; colorectal cancer; mucosal regeneration; immunology; gastroenterology; internal medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Currently, approximately 3–5% of the worldwide population is affected by autoimmune diseases (ADs), comprising over 150 different types, and both statistics are still increasing. Within the multifactorial etiology of chronic and self-perpetuating ADs with prominent inflammation, failure of self-tolerance and aberrant immune regulation seem to be especially deleterious. Thus, the basic therapeutic goal in ADs is to achieve immune homeostasis, i.e., the state of dynamic equilibrium, a balance between pro- and anti-inflammatory responses. Though treatment strategies have improved upon significant knowledge of AD pathogenesis, in some patients (mainly with refractory diseases) traditionally used immunosuppressive drugs fail to prevent relapses. Further, in parallel with long-term administration, harmful adverse effects, such as a higher risk of infection and increased tumor susceptibility, may occur. Therefore, as part of personalized medicine in ADs, the development of more specific and tolerable therapeutic options is required. Over the last 20 years, stem cell (SC) therapy (in forms of allogeneic or autologous hematopoietic (HSCs) and mesenchymal stem cells (MSCs)) has been considered to be a promising alternative approach. Besides repairing damaged tissues, SCs have the unique ability to modulate the immune system extensively in terms of immune reconstitution and overcoming the impaired self-tolerance status. In addition, MSC-derived extracellular vesicles (secretomes) play an important role in the regulation of innate and adaptive immune reactions as well. Upon these activities, SCs could serve as ideal therapeutic agents with the capacity to provide long-lasting, sustained protection from autoimmunity. However, in human ADs, most SC treatment methods are still in early phases, so further studies are required for an expected widespread clinical application. The purpose of this Special Issue is to discuss current trends of different stem cell-based therapy options in ADs, including their advantages, disadvantages, and obstacles, from a broad perspective of basic research and clinical practice.

Dr. Györgyi Műzes
Dr. Ferenc Sipos
Guest Editors

Manuscript Submission Information

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Keywords

  • autoimmune disease
  • stem cell therapy
  • hematopoietic stem cells
  • mesenchymal stem cells
  • MSC-derived secretome

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Related Special Issue

Published Papers (8 papers)

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Research

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14 pages, 2583 KiB  
Article
HLA-G and CD152 Expression Levels Encourage the Use of Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells as an Alternative for Immunosuppressive Therapy
by Bernardo Zoehler, Letícia Fracaro, Lidiane Maria Boldrini-Leite, José Samuel da Silva, Paul J. Travers, Paulo Roberto Slud Brofman, Maria da Graça Bicalho and Alexandra Cristina Senegaglia
Cells 2022, 11(8), 1339; https://doi.org/10.3390/cells11081339 - 14 Apr 2022
Cited by 5 | Viewed by 3051
Abstract
Mesenchymal stromal cells (MSCs) have been used in immunosuppressive therapy due to their therapeutic effects, with the HLA-G molecule seeming to play a fundamental role. This work evaluated alternative MSC sources to bone marrow (BM), namely, umbilical cord tissue (UC), adipose tissue (AD) [...] Read more.
Mesenchymal stromal cells (MSCs) have been used in immunosuppressive therapy due to their therapeutic effects, with the HLA-G molecule seeming to play a fundamental role. This work evaluated alternative MSC sources to bone marrow (BM), namely, umbilical cord tissue (UC), adipose tissue (AD) and dental pulp tissue (DP), and the influence of interferon-γ (IFN-γ) and hypoxia on the cultivation of these cells for use in immunosuppression therapies. Expression of costimulatory markers CD40, CD80 and CD86 and immunosuppressive molecules CD152 and HLA-G was analyzed. Lymphocyte inhibition assays were also performed. Sequencing of the HLA-G gene from exons 1 to 5 was performed using next-generation sequencing to determine the presence of alleles. UC-derived MSCs (UCMSCs) expressed higher CD152 and HLA-G1 under standard cultivation. UCMSCs and DP-derived MSCs (DPSCs) secreted similar levels of HLA-G5. All MSC sources inhibited the proliferation of peripheral blood mononuclear cells (PBMCs); growth under regular versus hypoxic conditions resulted in similar levels of inhibition. When IFN-γ was added, PBMC growth was inhibited to a lesser extent by UCMSCs. The HLA-G*01:04:01:01 allele appears to generate a more efficient MSC response in inhibiting lymphocyte proliferation. However, the strength of this conclusion was limited by the small sample size. UCMSCs are an excellent alternative to BM in immunosuppressive therapy: they express high concentrations of inhibitory molecules and can be cultivated without stimuli, which minimizes cost. Full article
(This article belongs to the Special Issue Stem Cell Therapy for Autoimmune Diseases)
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Review

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15 pages, 815 KiB  
Review
Human Hematopoietic Stem/Progenitor Cells in Type One Diabetes Mellitus Treatment: Is There an Ideal Candidate?
by Ermes Carulli, Giulio Pompilio and Maria Cristina Vinci
Cells 2023, 12(7), 1054; https://doi.org/10.3390/cells12071054 - 30 Mar 2023
Cited by 2 | Viewed by 1883
Abstract
Type 1 diabetes mellitus (T1DM) is a highly prevalent autoimmune disease causing the destruction of pancreatic islet β-cells. The resulting insulin production deficiency leads to a lifelong need for insulin re-placement therapy, systemic complications, and reduced life quality and expectancy. Cell therapy has [...] Read more.
Type 1 diabetes mellitus (T1DM) is a highly prevalent autoimmune disease causing the destruction of pancreatic islet β-cells. The resulting insulin production deficiency leads to a lifelong need for insulin re-placement therapy, systemic complications, and reduced life quality and expectancy. Cell therapy has been extensively attempted to restore insulin independence (IID), and autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) has appeared to give the most promising results, but with a highly variable quote of patients achieving IID across the studies. We performed a comprehensive review of the trials involving stem cells, and in particular AHST, for the treatment of T1DM. We then pooled the patients enrolled in the different trials and looked for the patient characteristics that could be associated with the achievement of IID. We found a significantly higher probability of achieving IID in older patients (OR 1.17, 95%CI 1.06–1.33, p = 0.002) and a significantly lower probability in patients with a history of ketoacidosis (OR 0.23, 95%CI 0.06–0.78, p = 0.023). This suggests that there could be a population of patients more likely to benefit from AHST, but further data would be required to depict the profile of the ideal candidate. Full article
(This article belongs to the Special Issue Stem Cell Therapy for Autoimmune Diseases)
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26 pages, 2440 KiB  
Review
Hematopoietic Cell Transplantation for Systemic Sclerosis—A Review
by Daniel Levin, Mohammed S. Osman, Caylib Durand, Hyein Kim, Iman Hemmati, Kareem Jamani, Jonathan G. Howlett, Kerri A. Johannson, Jason Weatherald, Matthew Woo, Jason Lee and Jan Storek
Cells 2022, 11(23), 3912; https://doi.org/10.3390/cells11233912 - 3 Dec 2022
Cited by 3 | Viewed by 2992
Abstract
Systemic sclerosis (SSc) is an autoimmune, multi-organ, connective tissue disease associated with significant morbidity and mortality. Conventional immunosuppressive therapies demonstrate limited efficacy. Autologous hematopoietic stem cell transplantation (HCT) is more efficacious but carries associated risks, including treatment-related mortality. Here, we review HCT as [...] Read more.
Systemic sclerosis (SSc) is an autoimmune, multi-organ, connective tissue disease associated with significant morbidity and mortality. Conventional immunosuppressive therapies demonstrate limited efficacy. Autologous hematopoietic stem cell transplantation (HCT) is more efficacious but carries associated risks, including treatment-related mortality. Here, we review HCT as a treatment for SSc, its efficacy and toxicity in comparison to conventional therapies, and the proposed mechanisms of action. Furthermore, we discuss the importance of and recent developments in patient selection. Finally, we highlight the knowledge gaps and future work required to further improve patient outcomes. Full article
(This article belongs to the Special Issue Stem Cell Therapy for Autoimmune Diseases)
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14 pages, 546 KiB  
Review
Hematopoietic Stem Cell Transplantation in Refractory Crohn’s Disease: Should It Be Considered?
by Simon Reider, Lukas Binder, Stefan Fürst, Stefan Hatzl and Andreas Blesl
Cells 2022, 11(21), 3463; https://doi.org/10.3390/cells11213463 - 2 Nov 2022
Cited by 5 | Viewed by 2216
Abstract
Hematopoietic stem cell transplantation (HSCT) is widely used in benign and malignant hematological diseases. During the last decade, HSCT, mainly autologous, also gained increasing attention in the treatment of refractory autoimmune diseases. Crohn’s disease (CD) is an inflammatory bowel disease leading to transmural [...] Read more.
Hematopoietic stem cell transplantation (HSCT) is widely used in benign and malignant hematological diseases. During the last decade, HSCT, mainly autologous, also gained increasing attention in the treatment of refractory autoimmune diseases. Crohn’s disease (CD) is an inflammatory bowel disease leading to transmural inflammation potentially affecting all parts of the luminal gastrointestinal tract. Despite improving therapeutic options, including various biologics, some patients are refractory to all lines of available conservative therapy, leading to increased morbidity and reduced quality of life. Apart from surgery, HSCT might be a reasonable treatment alternative for refractory CD patients. This review aims to describe the current role of HSCT in CD and discusses the procedure, the correct patient selection, the clinical efficacy from initial remission to following relapse rates, and complications of this treatment. Full article
(This article belongs to the Special Issue Stem Cell Therapy for Autoimmune Diseases)
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21 pages, 1838 KiB  
Review
Cellular-Based Therapies in Systemic Sclerosis: From Hematopoietic Stem Cell Transplant to Innovative Approaches
by Elisabetta Xue, Antonina Minniti, Tobias Alexander, Nicoletta Del Papa, Raffaella Greco and on behalf of The Autoimmune Diseases Working Party (ADWP) of the European Society for Blood and Marrow Transplantation (EBMT)
Cells 2022, 11(21), 3346; https://doi.org/10.3390/cells11213346 - 24 Oct 2022
Cited by 9 | Viewed by 3384
Abstract
Systemic sclerosis (SSc) is a systemic disease characterized by autoimmune responses, vasculopathy and tissue fibrosis. The pathogenic mechanisms involve a wide range of cells and soluble factors. The complexity of interactions leads to heterogeneous clinical features in terms of the extent, severity, and [...] Read more.
Systemic sclerosis (SSc) is a systemic disease characterized by autoimmune responses, vasculopathy and tissue fibrosis. The pathogenic mechanisms involve a wide range of cells and soluble factors. The complexity of interactions leads to heterogeneous clinical features in terms of the extent, severity, and rate of progression of skin fibrosis and internal organ involvement. Available disease-modifying drugs have only modest effects on halting disease progression and may be associated with significant side effects. Therefore, cellular therapies have been developed aiming at the restoration of immunologic self-tolerance in order to provide durable remissions or to foster tissue regeneration. Currently, SSc is recommended as the ‘standard indication’ for autologous hematopoietic stem cell transplantation by the European Society for Blood and Marrow Transplantation. This review provides an overview on cellular therapies in SSc, from pre-clinical models to clinical applications, opening towards more advanced cellular therapies, such as mesenchymal stem cells, regulatory T cells and potentially CAR-T-cell therapies. Full article
(This article belongs to the Special Issue Stem Cell Therapy for Autoimmune Diseases)
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23 pages, 3388 KiB  
Review
Mesenchymal Stem Cell-Derived Secretome: A Potential Therapeutic Option for Autoimmune and Immune-Mediated Inflammatory Diseases
by Györgyi Műzes and Ferenc Sipos
Cells 2022, 11(15), 2300; https://doi.org/10.3390/cells11152300 - 26 Jul 2022
Cited by 78 | Viewed by 8771
Abstract
Immune-mediated inflammatory diseases (IMIDs) encompass several entities such as “classic” autoimmune disorders or immune-mediated diseases with autoinflammatory characteristics. Adult stem cells including mesenchymal stem cells (MSCs) are by far the most commonly used type in clinical practice. However, due to the possible side [...] Read more.
Immune-mediated inflammatory diseases (IMIDs) encompass several entities such as “classic” autoimmune disorders or immune-mediated diseases with autoinflammatory characteristics. Adult stem cells including mesenchymal stem cells (MSCs) are by far the most commonly used type in clinical practice. However, due to the possible side effects of MSC-based treatments, there is an increase in interest in the MSC-secretome (containing large extracellular vesicles, microvesicles, and exosomes) as an alternative therapeutic option in IMIDs. A wide spectrum of MSC-secretome-related biological activities has been proven thus far including anti-inflammatory, anti-apoptotic, and immunomodulatory properties. In comparison with MSCs, the secretome is less immunogenic but exerts similar biological actions, so it can be considered as an ideal cell-free therapeutic alternative. Additionally, since the composition of the MSC-secretome can be engineered, for a future perspective, it could also be viewed as part of a potential delivery system within nanomedicine, allowing us to specifically target dysfunctional cells or tissues. Although many encouraging results from pre-clinical studies have recently been obtained that strongly support the application of the MSC-secretome in IMIDs, human studies with MSC-secretome administration are still in their infancy. This article reviews the immunomodulatory effects of the MSC-secretome in IMIDs and provides insight into the interpretation of its beneficial biological actions. Full article
(This article belongs to the Special Issue Stem Cell Therapy for Autoimmune Diseases)
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23 pages, 564 KiB  
Review
Stem Cell Therapy in Neuroimmunological Diseases and Its Potential Neuroimmunological Complications
by Franz Felix Konen, Philipp Schwenkenbecher, Konstantin Fritz Jendretzky, Stefan Gingele, Lea Grote-Levi, Nora Möhn, Kurt-Wolfram Sühs, Britta Eiz-Vesper, Britta Maecker-Kolhoff, Corinna Trebst, Thomas Skripuletz and Martin W. Hümmert
Cells 2022, 11(14), 2165; https://doi.org/10.3390/cells11142165 - 11 Jul 2022
Cited by 4 | Viewed by 3684
Abstract
Background: Since the 1990s, transplantations of hematopoietic and mesenchymal stem cells (HSCT and MSCT) and dendritic cell (DCT) have been investigated for the treatment of neurological autoimmune disorders (NADs). With the growing number of transplanted patients, awareness of neuroimmunolgical complications has increased. [...] Read more.
Background: Since the 1990s, transplantations of hematopoietic and mesenchymal stem cells (HSCT and MSCT) and dendritic cell (DCT) have been investigated for the treatment of neurological autoimmune disorders (NADs). With the growing number of transplanted patients, awareness of neuroimmunolgical complications has increased. Therefore, an overview of SCT for the most common NADs and reports of secondary immunity after SCT is provided. Methods: For this narrative review, a literature search of the PubMed database was performed. A total of 86 articles reporting on different SCTs in NADs and 61 articles dealing with immune-mediated neurological complications after SCT were included. For multiple sclerosis (MS), only registered trials and phase I/II or II studies were considered, whereas all available articles on other disorders were included. The different transplantation procedures and efficacy and safety data are presented. Results: In MS patients, beneficial effects of HSCT, MSCT, and DCT with a decrease in disability and stabilization of disease activity have been reported. These effects were also shown in other NADs mainly in case reports. In seven of 132 reported patients with immune-mediated neurological complications, the outcome was fatal. Conclusions: Phase III trials are ongoing for MS, but the role of SCT in other NADs is currently limited to refractory patients due to occasional serious complications. Full article
(This article belongs to the Special Issue Stem Cell Therapy for Autoimmune Diseases)
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15 pages, 320 KiB  
Review
Universal or Personalized Mesenchymal Stem Cell Therapies: Impact of Age, Sex, and Biological Source
by Diana M. Carp and Yun Liang
Cells 2022, 11(13), 2077; https://doi.org/10.3390/cells11132077 - 30 Jun 2022
Cited by 15 | Viewed by 3040
Abstract
Mesenchymal stem/stromal cells (MSCs) hold great promise for the treatment of autoimmune conditions given their immunomodulatory properties. Based on the low immunogenicity of MSCs, it is tempting to consider the expansion of MSCs from a “universal donor” in culture prior to their allogeneic [...] Read more.
Mesenchymal stem/stromal cells (MSCs) hold great promise for the treatment of autoimmune conditions given their immunomodulatory properties. Based on the low immunogenicity of MSCs, it is tempting to consider the expansion of MSCs from a “universal donor” in culture prior to their allogeneic applications for immediate care. This raises the critical question of the criteria we should use to select the best “universal donor”. It is also imperative we compare the “universal” approach with a “personalized” one for clinical value. In addition to the call for MHC-matching, recent studies suggest that factors including age, sex, and biological sources of MSCs can have significant impact on therapy outcome. Here, we will review findings from these studies, which shed light on the variables that can guide the important choice of “universal” or “personalized” MSC therapy for autoimmune diseases. Full article
(This article belongs to the Special Issue Stem Cell Therapy for Autoimmune Diseases)
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