Current Stem Cell Research & Therapy - Volume 18, Issue 6, 2023

Lymphatic vasculature plays essential role in interstitial tissue uptake, immune cell transport and dietary lipid absorption. Increasing evidence has demonstrated the contribution of lymphangiogenesis to tissue repair and regeneration, which is associated with multiple factors such as improved tissue homeostasis, inflammation resolution, and immunomodulation effects. Meanwhile, lymphangiogenesis has the potential to regulate cell growth and proliferation through paracrine effects. Lymphatic vessels can also be important components of the stem cell niche and participate in regulating stem cell quiescency or activity. In perspective, the functions and mechanisms of lymphatic vessels in tissue repair and regeneration deserve further investigation. Novel strategies to stimulate lymphangiogenesis by using pharmacological, genetic, and lymphatic tissue engineering will be prospective to promote tissue repair and regeneration.

Moyamoya disease (MMD) is a chronic steno-occlusion cerebrovascular disease accompanied by the formation of the abnormal vascular network at the base of the brain. The etiology of MMD is not fully clarified. Lack of pathological specimens hinders the research progress. Induced pluripotent stem cells (iPSC) derived from patients with outstanding differentiation potential and infinite proliferation ability could conquer the problem of insufficient samples. The technology of iPSC holds the promise of clarifying the underlying molecular mechanism in the development of MMD. In this review, we summarized the latest progress and difficulties in the research of mechanism and detailed the application of iPSC in MMD, aiming to provide an outlook of iPSC in molecular mechanism and novel therapies of MMD.

The bovine mammary gland has vital importance in the dairy sector, as it is considered a source of basic dairy product, milk. Mammary gland affections are widespread, which affect the dairy industry economically and pose a potential public health hazard. Current therapeutic options are ineffective in controlling the infection and regenerating the gland effectively. Antimicrobials commonly used against mastitis make their way into the milk . In order to find a solution to these problems, advanced therapeutic options, like the one for stem cells, are considered. Mammary gland stem cells (MaSCs) are considered to maintain tissue homeostasis. The characterization of these cells and their derived lineages (progenitor cells and mammary epithelial cells) may potentially provide the physiological status or production potential of the gland. However, current isolation methods are cumbersome and fall short to isolate a pure line of cattle MaSCs from progenitors or other differentiated epithelial cells. An alternative to the therapeutic application of MaSCs is the mesenchymal stem cell (MSC). These cells can potentially control microbial infection, show anti-inflammatory and other pro-healing effects, and furthermore enhance mammary epithelial cell secretory potential to ensure tissue regeneration. The current review focuses on MaSCs and MSCs properties in light of the bovine mammary gland regeneration.

Cancer stem cells (CSCs) are transformed forms of normal stem cells within heterogeneous mixture of cancer cells. These are mainly responsible for the recurrence of cancer after treatment because of their ability to develop resistance against chemo and radiotherapy due to various factors such as activation of signalling pathways important for self-renewal, DNA repair capacity, microenvironment and expression of ABC transporters. Targeting these mechanisms as potential factors can eliminate CSCs, which eventually decreases cancer recurrence. This review focuses on the characteristics of CSCs, their role in the development of resistance to chemotherapy and radiotherapy along with the therapeutic potential targets for successful elimination of CSC population.

With a booming aging population worldwide, bone and joint degenerative diseases have gradually become a major public health focus, attracting extensive scientific attention. However, the effective treatments of these degenerative diseases have been confined to traditional medications and surgical interventions, which easily lead to the possibility of drug abuse or loss of physiological function to varying degrees. Recently, given that the development of reprogramming has overcome shackles in the field of degenerative diseases, direct reprogramming would provide a new concept to accelerate progress in the therapy of bone and joint degenerative diseases. The process of direct reprogramming would directly induce ordinary somatic cells to the desired targeted cells without passing through pluripotent cell states. In this review, we summarize some direct reprogramming of cells that has been attempted for the repair of common bone and joint degenerative diseases, such as osteoarthritis, osteoporosis-related fracture and intervertebral disc degeneration. However, it is inevitable that some obstacles, such as accurate transcription factors, an appropriate extracellular microenvironment and efficient delivery carriers in vivo, need to be resolved. In addition, developmental and promising directions associated with direct reprogramming have attracted public attention. Investigation of the regulation of the transient genome, metabolic conversion and cellular skeleton would provide superior potential candidates for the revolution of direct reprogramming. The aim of direct reprogramming is to directly provide target cells for cell therapy and even tissue reconstruction in bone and joint degenerative diseases. Moreover, the development of direct reprogramming have potential to achieve repair and even reconstruct in situ, which would be breakthrough effect for the repair of bone and joint degenerative diseases. The advance of direct reprogramming has opened numerous opportunities for new therapeutic strategies in regenerative medicine.

Background: Mesenchymal stem cells (MSCs) have been shown to decrease inflammation and enhance healing due to their immunomodulatory properties and secretion of growth factors. Intravenous infusion is the most common delivery route of MSCs, and it is used for the treatment of a wide variety of conditions, with established efficacy. Objective: This review will analyze the safety of intravenous infusion of MSCs and determine the incidence of any possible resultant Serious Adverse Events (SAEs). Methods: Using PubMed, we searched the scientific literature to identify SAEs related to intravenous infusion of MSCs. We performed disease-specific searches and a general adverse event search. Results: A total of 70 studies were included in this review. Thousands of infusions were administered and only two SAEs were identified from the same study. The SAEs were two upper extremity thromboembolisms in patients with preexisting renal disease. Conclusion: Properly performed intravenous infusion of MSCs is very safe, with a near absence of reported serious adverse events associated with its use.

Breast cancer stem cells (BCSCs) are heterogeneous tumor-initiating cell subgroups of breast cancers that possess some stem cell markers and are sustained after chemotherapy. Due to BCSCs being sufficient for tumor relapse, and given that the biological behaviors of BCSCs are so complex, it is critical to figure out exactly how they work, learn more about their cell biology, and discover biomarkers and strategies for explicitly targeting and destructing cancer stem cells. In order to accomplish innovative treatment for breast cancer, it is also essential to target BCSCs. Despite the vast quantities of BCSC target chemicals, their therapeutic implementation is limited due to off-target behavior and bioavailability issues. Targeted drug delivery systems based on nanoparticles have advantages for transporting anti-BCSC materials, especially to targeted locations. Hence, breast cancer therapy using a nanoparticle-based BCSCs targeting system is a promising strategy. Such targeted drug delivery systems can resolve the biodistribution obstacles of nanosystems. Throughout this paper, we highlight various strategies for targeting BCSCs utilizing nano-based systems. In conclusion, issues about the inadequate stability of nanoparticles and the possibility of loaded drug leakage during delivery systems have yet to be answered. More fundamental and applied research, and proper methods such as coating or surface modification are required.

Concurrent with the global outbreak of COVID-19, the race began among scientists to generate effective therapeutics for the treatment of COVID-19. In this regard, advanced technology such as nanotechnology, cell-based therapies, tissue engineering and regenerative medicine, nerve stimulation and artificial intelligence (AI) are attractive because they can offer new solutions for the prevention, diagnosis and treatment of COVID-19. Nanotechnology can design rapid and specific tests with high sensitivity for detecting infection and synthases new drugs and vaccines based on nanomaterials to directly deliver the intended antiviral agent to the desired site in the body and also provide new surfaces that do not allow virus adhesion. Mesenchymal stem cells and exosomes secreted from them apply in regenerative medicine and regulate inflammatory responses. Cell therapy and tissue engineering are combined to repair or substitute damaged tissues or cells. Tissue engineering using biomaterials, cells, and signaling molecules can develop new therapeutic and diagnostic platforms and help scientists fight viral diseases. Nerve stimulation technology can augment body's natural ability to modulate the inflammatory response and inhibit pro-inflammatory cytokines and consequently suppress cytokine storm. People can access free online health counseling services through AI and it helps very fast for screening and diagnosis of COVID-19 patients. This study is aimed first to give brief information about COVID-19 and the epidemiology of the disease. After that, we highlight important developments in the field of advanced technologies relevant to the prevention, detection, and treatment of the current pandemic.

Background: Mesenchymal stem cells (MSCs) are partially differentiated multipotent cells. They can be derived from various tissues such as the umbilical cord, bone marrow, and adipose tissue. Intrathecal administration of MSCs has shown efficacy for various neurological conditions including multiple sclerosis, autism, traumatic brain injury, and many more. Objective: This review will seek to determine whether there are any serious adverse events associated with spinal intrathecal administration of MSCs. Methods: PubMed was used to search the scientific literature for serious adverse events that are related to spinal intrathecal administration of MSCs. Disease specific searches were performed for neurological conditions that could benefit from intrathecal administration of MSCs. In addition, a general serious adverse events search was performed to identify any additional adverse events. Results and Discussion: A total of 39 studies were included in our analysis. None of the studies reported serious adverse events related to spinal intrathecal administration of MSCs. Notably, no infections, clinical rejection, or tumors were identified. Conclusion: Properly performed spinal intrathecal injection of MSCs is exceedingly safe, with no serious adverse events reported based on our exhaustive literature search.

Background: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a severe complication with a poor prognosis. Recently, mesenchymal stem cell (MSC)-based therapy for HBVACLF has shown considerable promise. Therefore, this systematic review and meta-analysis aimed to evaluate the efficacy and safety of MSC transplantation for patients with HBV-ACLF. Methods: The PubMed, Cochrane Library, CNKI, and Embase databases were searched from their inception to March 2021 for reports on MSC therapy for HBV-ACLF. We used RevMan 5.3 to perform the systematic review and meta-analysis. Results: Four studies were ultimately included. Compared with the control treatment, allogeneic MSC treatment resulted in a higher cumulative survival rate among ACLF patients (OR=2.27; 95% CI 1.35, 3.81; p=0.002). The umbilical cord-derived MSC (UC-MSC) group obtained a higher survival rate than the control group (OR = 2.33; 95% CI 1.17, 4.63; p=0.02). The group with multiple interval peripheral vein injections of MSCs obtained a higher survival rate than the control group (OR = 2.09; 95% CI 1.20, 3.67; p=0.01). None of the adverse events were MSC-related. Conclusion: Our study indicates that MSC transplantation can significantly increase survival rates by improving liver function without severe adverse events. UC-MSCs harvested for allogeneic infusion via peripheral veins appear to provide superior treatment for patients.

Background: The cardiomyocytes pyroptosis and bone marrow-derived mesenchymal stem cells have been well considered as novel therapies to attenuate myocardial ischemia/reperfusion injury, however, the relationship has not yet been determined. Objective: We aim to evaluate whether pre-treatment bone marrow-derived mesenchymal stem cells protect against myocardial ischemia/reperfusion injury by repressing cardiomyocytes pyroptosis, as well as to further elucidate the potential mechanisms. Methods: Cardiomyocytes were treated with hypoxia, followed by reoxygenation to mimic myocardial ischemia/reperfusion injury. Pre-treatment bone marrow-derived mesenchymal stem cells or their exosomes were co-cultured with cardiomyocytes following hypoxia/reoxygenation. Cell Counting Kit-8 assay was used to determine cell viability. Reactive oxygen species production was determined by dihydroethidium stain. Enzyme-linked immunosorbent assays were used to detect IL-1β and IL-18. Results: We observed that Irisin pre-treatment bone marrow-derived mesenchymal stem cells protected cardiomyocytes against hypoxia/reoxygenation-induced injuries. The underlying molecular mechanism was further identified. Irisin-BMMSCs were found to secrete exosomes, which repressed cardiomyocytes pyroptosis and oxidative stress response by suppressing NLRP3 under hypoxia/reoxygenation conditions. Conclusion: Based on our findings, we revealed a promising target that exosomes derived from bone marrow-derived mesenchymal stem cells with Irisin treatment to elevate the therapeutic benefits for hypoxia/ reoxygenation injury.

Introduction: Resident mesenchymal stem cells (MSCs) in the tumor microenvironment play an important role in tumor progression. Up to now, the mechanism of resident MSCs promoting gastric cancer cell migration remains unclear. Methods: We tested the migration ability of gastric cancer cells by transwell assays in this study. The inflammatory factors secreted by MSCs were detected by Luminex and ELISA. The activation of NF-ΚB signaling was detected by western blot. The exosomes derived from MSCs were isolated and identified by transmission electron microscope, nano-sight and western blot. The expression of miR-374a-5p was confirmed by qRT-PCR and its downstream target HAPLN1 by luciferase reporter assay. The expression of adhesion molecules of gastric cancer cells was detected by flow cytometry. Results: MiR-374a-5p could regulate the expression of inflammatory factors by activating NF-ΚB signaling. The increase of MCP-1 and the decrease of IFN-γ promoted the migration of gastric cancer cells. The miR-374a-5p in MSCs could be encapsulated and delivered to gastric cancer cells by exosomes derived from MSCs. Exogenous miR-374a-5p up-regulated the expression of adhesion molecules in gastric cancer cells by targeting HAPLN1. And miR-374a-5p-enriched exosomes also promoted the migration of gastric cancer cells. Conclusion: MiR-374a-5p promoted gastric cancer metastasis, and resident MSCs in the gastric cancer microenvironment played a major role in the regulation of gastric cancer metastasis. The study will provide new ideas and potential targets for the prevention and treatment of gastric cancer metastasis.

Background: Acute skeletal muscle injuries are common physical or sports traumas. Cellular therapy has excellent potential for regeneration after skeletal muscle injury. Adipose-derived stem cells (ADSCs) are a more accessible type of stem cell. However, it has a low survival rate and differentiation efficiency in the oxidative stress-rich microenvironment after transplantation. Although molecular hydrogen (H2) possesses anti-inflammatory and antioxidant biological properties, its utility in mitochondrial and stem cell research has not been adequately explored. Objective: This study aimed to reveal the role of H 2on adipose-derived stem cells' myogenic differentiation. Methods: The protective effects of H 2in ADSCs were evaluated by MTT assay, live-dead cell staining, western blot analysis, immunofluorescence staining, confocal imaging, and transmission electron microscopy. Results: An appropriate volume fraction of H 2significantly decreased mitochondrial reactive oxygen species (ROS) levels, increased the number of mitochondria, and promoted mitophagy, thus enhancing the survival and myogenic differentiation of ADSCs. Conclusion: This study reveals the application potential of H 2in skeletal muscle diseases or other pathologies related to mitochondrial dysfunction.