Mesenchymal Stem Cell Therapy in Diabetic Cardiomyopathy

The incidence and prevalence of diabetes mellitus (DM) are increasing worldwide, and the resulting cardiac complications are the leading cause of death. Among these complications is diabetes-induced cardiomyopathy (DCM), which is the consequence of a pro-inflammatory condition, oxidative stress and fibrosis caused by hyperglycemia. Cardiac remodeling will lead to an imbalance in cell survival and death, which can promote cardiac dysfunction. Since the conventional treatment of DM generally does not address the prevention of cardiac remodeling, it is important to develop new alternatives for the treatment of cardiovascular complications induced by DM. Thus, therapy with mesenchymal stem cells has been shown to be a promising approach for the prevention of DCM because of their anti-apoptotic, anti-fibrotic and anti-inflammatory effects, which could improve cardiac function in patients with DM.

Metabolic Rewiring by Human Placenta-Derived Mesenchymal Stem Cell Therapy Promotes Rejuvenation in Aged Female Rats

Aging is a degenerative process involving cell function deterioration, leading to altered metabolic pathways, increased metabolite diversity, and dysregulated metabolism. Previously, we reported that human placenta-derived mesenchymal stem cells (hPD-MSCs) have therapeutic effects on ovarian aging. This study aimed to identify hPD-MSC therapy-induced responses at the metabolite and protein levels and serum biomarker(s) of aging and/or rejuvenation. We observed weight loss after hPD-MSC therapy. Importantly, insulin-like growth factor-I (IGF-I), known prolongs healthy life spans, were markedly elevated in serum. Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS) analysis identified 176 metabolites, among which the levels of 3-hydroxybutyric acid, glycocholic acid, and taurine, which are associated with health and longevity, were enhanced after hPD-MSC stimulation. Furthermore, after hPD-MSC therapy, the levels of vitamin B6 and its metabolite pyridoxal 5′-phosphate were markedly increased in the serum and liver, respectively. Interestingly, hPD-MSC therapy promoted serotonin production due to increased vitamin B6 metabolism rates. Increased liver serotonin levels after multiple-injection therapy altered the expression of mRNAs and proteins associated with hepatocyte proliferation and mitochondrial biogenesis. Changes in metabolites in circulation after hPD-MSC therapy can be used to identify biomarker(s) of aging and/or rejuvenation. In addition, serotonin is a valuable therapeutic target for reversing aging-associated liver degeneration.

Making More Womb: Clinical Perspectives Supporting the Development and Utilization of Mesenchymal Stem Cell Therapy for Endometrial Regeneration and Infertility

The uterus is a homeostatic organ, unwavering in the setting of monthly endometrial turnover, placental invasion, and parturition. In response to ovarian steroid hormones, the endometrium autologously prepares for embryo implantation and in its absence will shed and regenerate. Dysfunctional endometrial repair and regeneration may present clinically with infertility and abnormal menses. Asherman’s syndrome is characterized by intrauterine adhesions and atrophic endometrium, which often impacts fertility. Clinical management of infertility associated with abnormal endometrium represents a significant challenge. Endometrial mesenchymal stem cells (MSC) occupy a perivascular niche and contain regenerative and immunomodulatory properties. Given these characteristics, mesenchymal stem cells of endometrial and non-endometrial origin (bone marrow, adipose, placental) have been investigated for therapeutic purposes. Local administration of human MSC in animal models of endometrial injury reduces collagen deposition, improves angiogenesis, decreases inflammation, and improves fertility. Small clinical studies of autologous MSC administration in infertile women with Asherman’s Syndrome suggested their potential to restore endometrial function as evidenced by increased endometrial thickness, decreased adhesions, and fertility. The objective of this review is to highlight translational and clinical studies investigating the use of MSC for endometrial dysfunction and infertility and to summarize the current state of the art in this promising area.

Method Categorization of Stem Cell Therapy for Degenerative Osteoarthritis of the Knee: A Review

Current clinical applications of mesenchymal stem cell therapy for osteoarthritis lack consistency because there are no established criteria for clinical processes. We aimed to systematically organize stem cell treatment methods by reviewing the literature. The treatment methods used in 27 clinical trials were examined and reviewed. The clinical processes were separated into seven categories: cell donor, cell source, cell preparation, delivery methods, lesion preparation, concomitant procedures, and evaluation. Stem cell donors were sub-classified as autologous and allogeneic, and stem cell sources included bone marrow, adipose tissue, peripheral blood, synovium, placenta, and umbilical cord. Mesenchymal stem cells can be prepared by the expansion or isolation process and attached directly to cartilage defects using matrices or injected into joints under arthroscopic observation. The lesion preparation category can be divided into three subcategories: chondroplasty, microfracture, and subchondral drilling. The concomitant procedure category describes adjuvant surgery, such as high tibial osteotomy. Classification codes were assigned for each subcategory to provide a useful and convenient method for organizing documents associated with stem cell treatment. This classification system will help researchers choose more unified treatment methods, which will facilitate the efficient comparison and verification of future clinical outcomes of stem cell therapy for osteoarthritis.

Does intra-articular injection of adipose-derived stem cells improve cartilage mass? A case report using three-dimensional image analysis software in knee osteoarthritis

Background Mesenchymal stem cells are currently a research focus because of the possibility of cartilage regeneration through several mechanisms, including mesenchymal stem cell sheets. However, there are no published reports visualizing cartilage in three dimensions. Here, we report a case of improved cartilage volume. We purified and cultured adipose-derived mesenchymal stem cells and then performed adipose-derived mesenchymal stem cell therapy by directly injecting these cells into the articular cartilage. Cartilage was quantitatively evaluated before and after injection using three-dimensional image analysis software based on the magnetic resonance imaging. Case presentation The patient, a 55-year-old Japanese woman, experienced pain in both knees and was diagnosed with osteoarthritis of the knee. We performed adipose-derived mesenchymal stem cell therapy in both knees at our hospital and quantitatively evaluated cartilage before and after the treatment using the three-dimensional image analysis software “SYNAPSE VINCENT”. Conclusions Preoperatively, the cartilage defect area was 33.59 mm2 in the femur and 122.31 mm2 in the tibia; however, 12 months postoperatively, it improved to 13.59 mm2 and 51.43 mm2, respectively. Furthermore, the preoperative femur and tibia volumes were 9.58 mL and 3.82 mL, respectively; however, 12 months postoperatively, these values improved to 10.00 mL and 4.17 mL, respectively. For the quantitative analysis of cartilage, SYNAPSE VINCENT visualizes the state of cartilage in a high-definition three-dimensional image, which is excellent for understanding the state of the disease and explaining it to the patient. Although SYNAPSE VINCENT can only analyze the thickness of cartilage, and the reproducibility of the error is debatable, SYNAPSE VINCENT would be useful as a clinical tool for regenerative medicine. We have shown in this case report the promising effects of adipose-derived stem cell intraarticular injections in treating osteoarthritis and the use of new diagnostic instruments.

Will Mesenchymal Stem Cell Therapy Be Effective In COVID-19?

Background: The World Health Organization (WHO) reports that the outbreak of the deadly virus had been noted almost in all the countries worldwide. Newly no standard therapies are available to combat the situation and this remains the major challenge for healthcare professionals to provide effective treatment against the life-threatening condition. A potential regenerative medicine method using the infusion of stem cells for the treatment of lung disorders has been reported. This review attempted to explore the immunomodulatory characteristics of Mesenchymal Stem Cells (MSCs) and how these properties make them beneficial for the treatment of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) patients. Objectives: To study the effect of Mesenchymal Stem Cell therapy in treating COVID-19. Methodology: A literature search was conducted to identify recent research relating to the review's goal of analyzing the relevance of stem cells in battling SARS-CoV-2. Results: The MSCs settle in the lungs intravenously to enhance the pulmonary microenvironment, minimize immune system over-activation, and encourage regeneration of damaged lung tissues. Its therapeutic properties like immune response inhibition play a major role in combating viruses. The avoidance of cytokine storm is the most important stage in COVID-19 therapy. Their potent immunomodulatory properties have positive effects in avoiding or attenuating the cytokine storm and assisting in the regeneration of injured lung tissues/other organs. Conclusion: Intravenous human Umbilical Cord-Mesenchymal Stem Cell therapy (hUC-MSC) transplantation is a safe and effective technique that may be used as a restoration and prioritized therapeutic option for treating severe COVID-19. Keywords: Covid-19, human Umbilical Cord-Mesenchymal Stem Cell therapy (huc-msc), Immune system.

The Role of Mesenchymal Stem Cell Therapy in Traumatic Brain Injury: A Review from Basic Research to Clinical Challenges

<p>Traumatic brain injury (TBI) is a focal injury with limited reliable treatment options. Despite the large volume of basic research into TBI (particularly on the complex pathophysiology and on the application of various techniques), the treatment of TBI currently remains a challenge due to the low efficacy of available therapeutic options. Recent studies have shown that stem cells possess the ability to aid in recovery from the damaging effects of the craniocerebral injury. Herein, we attempted to present a generalized critique for the role of mesenchymal stem cell therapy in TBI, its underlying mechanisms, and the scope for improvements in TBI treatment identified through preclinical studies, clinical studies, and other research in the light of previously reported literature. Finally, we summarized some novel strategies to overcome the clinical challenges in TBI recovery. Collectively, the major objective of this review is to highlight the to-date available findings regarding role of stem cell therapy in TBI and pave the way for the development of safe and efficient regenerative treatment modalities for TBI by comprehensive understanding the specific mechanism.</p>