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Advanced Research in Stem Cell and Exosome-Based Therapy
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Advanced Research in Stem Cell and Exosome-Based Therapy

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 (20 June 2024) | Viewed by 12211

Special Issue Editor

Dr. Yuanyuan Zhang

E-Mail Website
Guest Editor
Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC 27101, USA
Interests: stem cells; exosomes; gene therapy; tissue engineering; 3D organoids; biomaterials; regenerative medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Stem cells, as a large group of cells with multi-directional differentiation and self-renewal ability, have recently played a pivotal role in life sciences. In addition to inducing various types of stem cells for regenerative medicine and tissue engineering, the microenvironment around stem cells and cancer stem cells have also attracted widespread attention. Exosomes are extracellular vesicles that are secreted by almost all cells and have a diameter of 30 to 100 nm. They usually contain cell-active components such as proteins and nucleic acids from the cells that secrete them. Since the contents of exosomes can reflect the various characteristics of the cells from which they are derived, whether the powerful functions of stem cells are related to their exosomes is also a hot topic.

This Special Issue welcomes research related to stem cell and exosome-based therapy, including, but not limited to, cardiovascular disease, respiratory/pulmonary disease and injury, spinal cord injury, type 1 diabetes, sepsis, Parkinson's disease, ALS, Alzheimer's disease, stroke, burns, cancer, and musculoskeletal disease.

Dr. Yuanyuan Zhang
Guest Editor

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Published Papers (5 papers)

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Research

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26 pages, 13906 KiB  
Article
In Vitro Gene Therapy Using Human iPS-Derived Mesoangioblast-Like Cells (HIDEMs) Combined with Microdystrophin (μDys) Expression as the New Strategy for Duchenne Muscular Dystrophy (DMD) Experimental Treatment
by Marta Budzińska, Agnieszka Malcher, Agnieszka Zimna and Maciej Kurpisz
Int. J. Mol. Sci. 2024, 25(22), 11869; https://doi.org/10.3390/ijms252211869 - 5 Nov 2024
Viewed by 970
Abstract
Duchenne Muscular Dystrophy (DMD) is a genetic disorder characterized by disruptions in the dystrophin gene. This study aims to investigate potential a therapeutic approach using genetically modified human iPS-derived mesoangioblast-like cells (HIDEMs) in mdx mouse model. This study utilizes patient-specific myoblasts reprogrammed to [...] Read more.
Duchenne Muscular Dystrophy (DMD) is a genetic disorder characterized by disruptions in the dystrophin gene. This study aims to investigate potential a therapeutic approach using genetically modified human iPS-derived mesoangioblast-like cells (HIDEMs) in mdx mouse model. This study utilizes patient-specific myoblasts reprogrammed to human induced pluripotent stem cells (iPSCs) and then differentiated into HIDEMs. Lentiviral vectors carrying microdystrophin sequences have been employed to deliver the genetic construct to express a shortened, functional dystrophin protein in HIDEMs. The study indicated significant changes within redox potential between healthy and pathological HIDEM cells derived from DMD patients studied by catalase and superoxide dismutase activities. Microdystrophin expressing HIDEMs also improved expression of genes involved in STARS (striated muscle activator of Rho signaling) pathway albeit in selective DMD patients (with mild phenotype). Although in vivo observations did not bring progress in the mobility of mdx mice with HIDEMs, microdystrophin interventions this may argue against “treadmill test” as suitable for assessment of mdx mice recovery. Low-level signaling of the Rho pathway and inflammation-related factors in DMD myogenic cells can also contribute to the lack of success in a functional study. Overall, this research contributes to the understanding of DMD pathogenesis and provides insights into potential novel therapeutic strategy, highlighting the importance of personalized gene therapy. Full article
(This article belongs to the Special Issue Advanced Research in Stem Cell and Exosome-Based Therapy)
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18 pages, 3955 KiB  
Article
Assessment of Genetic Stability in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes by Using Droplet Digital PCR
by Ji Won Park, Su Ji Bae, Jun Ho Yun, Sunhee Kim and Misun Park
Int. J. Mol. Sci. 2024, 25(2), 1101; https://doi.org/10.3390/ijms25021101 - 16 Jan 2024
Cited by 2 | Viewed by 2252
Abstract
Unintended genetic modifications that occur during the differentiation and proliferation of human induced pluripotent stem cells (hiPSCs) can lead to tumorigenicity. This is a crucial concern in the development of stem cell-based therapies to ensure the safety and efficacy of the final product. [...] Read more.
Unintended genetic modifications that occur during the differentiation and proliferation of human induced pluripotent stem cells (hiPSCs) can lead to tumorigenicity. This is a crucial concern in the development of stem cell-based therapies to ensure the safety and efficacy of the final product. Moreover, conventional genetic stability testing methods are limited by low sensitivity, which is an issue that remains unsolved. In this study, we assessed the genetic stability of hiPSCs and hiPSC-derived cardiomyocytes using various testing methods, including karyotyping, CytoScanHD chip analysis, whole-exome sequencing, and targeted sequencing. Two specific genetic mutations in KMT2C and BCOR were selected from the 17 gene variants identified by whole-exome and targeted sequencing methods, which were validated using droplet digital PCR. The applicability of this approach to stem cell-based therapeutic products was further demonstrated with associated validation according to the International Council for Harmonisation (ICH) guidelines, including specificity, precision, robustness, and limit of detection. Our droplet digital PCR results showed high sensitivity and accuracy for quantitatively detecting gene mutations, whereas conventional qPCR could not avoid false positives. In conclusion, droplet digital PCR is a highly sensitive and precise method for assessing the expression of mutations with tumorigenic potential for the development of stem cell-based therapeutics. Full article
(This article belongs to the Special Issue Advanced Research in Stem Cell and Exosome-Based Therapy)
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9 pages, 1184 KiB  
Article
Persistent Hypogammaglobulinemia after Receiving Rituximab Post-HSCT Is Not Caused by an Intrinsic B Cell Defect
by Lisa M. Ott de Bruin, Ingrid Pico-Knijnenburg, Monique M. van Ostaijen-ten Dam, Thomas J. Weitering, Dagmar Berghuis, Robbert G. M. Bredius, Arjan C. Lankester and Mirjam van der Burg
Int. J. Mol. Sci. 2023, 24(21), 16012; https://doi.org/10.3390/ijms242116012 - 6 Nov 2023
Cited by 2 | Viewed by 2357
Abstract
In the setting of hematopoietic stem cell transplantation (HSCT), Rituximab (RTX) is used for the treatment and prevention of EBV-associated post-transplantation lymphoproliferative disease or autoimmune phenomena such as autoimmune hemolytic anemia (AIHA). Persistent hypogammaglobulinemia and immunoglobulin substitution dependence has been observed in several [...] Read more.
In the setting of hematopoietic stem cell transplantation (HSCT), Rituximab (RTX) is used for the treatment and prevention of EBV-associated post-transplantation lymphoproliferative disease or autoimmune phenomena such as autoimmune hemolytic anemia (AIHA). Persistent hypogammaglobulinemia and immunoglobulin substitution dependence has been observed in several patients after RTX treatment despite the normalization of total B cell numbers. We aimed to study whether this is a B cell intrinsic phenomenon. We analyzed four patients with different primary diseases who were treated with myeloablative conditioning and matched unrelated donor HSCT who developed persistent hypogammaglobulinemia after receiving RTX treatment. They all received RTX early after HSCT to treat EBV infection or AIHA post-HSCT. All patients showed normalized total B cell numbers but absent to very low IgG positive memory B cells, and three lacked IgA positive memory B cells. All of the patients had full donor chimerism, and none had encountered graft-versus-host disease. Sorted peripheral blood naïve B cells from these patients, when stimulated with CD40L, IL21, IL10 and anti-IgM, demonstrated intact B cell differentiation including the formation of class-switched memory B cells and IgA and IgG production. Peripheral blood T cell numbers including CD4 follicular T-helper (Tfh) cells were all within the normal reference range. In conclusion, in these four HSCT patients, the persistent hypogammaglobulinemia observed after RTX cannot be attributed to an acquired intrinsic B cell problem nor to a reduction in Tfh cell numbers. Full article
(This article belongs to the Special Issue Advanced Research in Stem Cell and Exosome-Based Therapy)
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Review

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13 pages, 914 KiB  
Review
The Use of Hematopoietic Stem Cells for Heart Failure: A Systematic Review
by Jayant Seth, Sohat Sharma, Cameron J. Leong, Venkat Vaibhav, Pierce Nelson, Arveen Shokravi, Yuchen Luo, Daniel Shirvani and Zachary Laksman
Int. J. Mol. Sci. 2024, 25(12), 6634; https://doi.org/10.3390/ijms25126634 - 17 Jun 2024
Viewed by 2199
Abstract
The purpose of this review is to summarize the current understanding of the therapeutic effect of stem cell-based therapies, including hematopoietic stem cells, for the treatment of ischemic heart damage. Following PRISMA guidelines, we conducted electronic searches in MEDLINE, and EMBASE. We screened [...] Read more.
The purpose of this review is to summarize the current understanding of the therapeutic effect of stem cell-based therapies, including hematopoietic stem cells, for the treatment of ischemic heart damage. Following PRISMA guidelines, we conducted electronic searches in MEDLINE, and EMBASE. We screened 592 studies, and included RCTs, observational studies, and cohort studies that examined the effect of hematopoietic stem cell therapy in adult patients with heart failure. Studies that involved pediatric patients, mesenchymal stem cell therapy, and non-heart failure (HF) studies were excluded from our review. Out of the 592 studies, 7 studies met our inclusion criteria. Overall, administration of hematopoietic stem cells (via intracoronary or myocardial infarct) led to positive cardiac outcomes such as improvements in pathological left-ventricular remodeling, perfusion following acute myocardial infarction, and NYHA symptom class. Additionally, combined death, rehospitalization for heart failure, and infarction were significantly lower in patients treated with bone marrow-derived hematopoietic stem cells. Our review demonstrates that hematopoietic stem cell administration can lead to positive cardiac outcomes for HF patients. Future studies should aim to increase female representation and non-ischemic HF patients. Full article
(This article belongs to the Special Issue Advanced Research in Stem Cell and Exosome-Based Therapy)
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22 pages, 819 KiB  
Review
Adipose-Derived Stem Cells: Angiogenetic Potential and Utility in Tissue Engineering
by Felor Biniazan, Alina Stoian and Siba Haykal
Int. J. Mol. Sci. 2024, 25(4), 2356; https://doi.org/10.3390/ijms25042356 - 16 Feb 2024
Cited by 12 | Viewed by 3310
Abstract
Adipose tissue (AT) is a large and important energy storage organ as well as an endocrine organ with a critical role in many processes. Additionally, AT is an enormous and easily accessible source of multipotent cell types used in our day for all [...] Read more.
Adipose tissue (AT) is a large and important energy storage organ as well as an endocrine organ with a critical role in many processes. Additionally, AT is an enormous and easily accessible source of multipotent cell types used in our day for all types of tissue regeneration. The ability of adipose-derived stem cells (ADSCs) to differentiate into other types of cells, such as endothelial cells (ECs), vascular smooth muscle cells, or cardiomyocytes, is used in tissue engineering in order to promote/stimulate the process of angiogenesis. Being a key for future successful clinical applications, functional vascular networks in engineered tissue are targeted by numerous in vivo and ex vivo studies. The article reviews the angiogenic potential of ADSCs and explores their capacity in the field of tissue engineering (TE). Full article
(This article belongs to the Special Issue Advanced Research in Stem Cell and Exosome-Based Therapy)
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