Journal of Stem Cells & Regenerative Medicine最新文献

Objective: In this study, we analyzed the therapeutic effect of periurethral injection of autologous muscle-derived stem cell versus mid-urethral sling surgery at a 1-year follow-up.

Method: This randomized controlled clinical trial was conducted on 30 women with stress urinary incontinence (SUI) who had not responded to conservative treatments, after registering the participants and obtaining informed consent. Patients were divided into two groups of 15 each treated with periurethral injection of muscle-derived stem cells (MDSCs) and mid-urethral sling surgery, respectively. Follow-ups were done at 1, 3, 6, and 12 months after the treatment using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UISF) and Incontinence Quality of Life Questionnaire (I-QOL) questionnaires, clinical examination, cough test, and 1-hour pad test. The results were analyzed within the groups and then compared between the two groups. Moreover, both groups were compared in terms of postoperative complications.

Results: At the 1-year follow-up, in the stem cell group, 10 patients (66.6%) experienced improvements after the periurethral injection of stem cells; half of these patients (33.3%) reported a full recovery. In the mid-urethral sling group, 13 patients (93.3%) experienced improvement, and 12 patients (80%) reported a full recovery. The analysis of ICIQ-UISF and I-QOL questionnaires indicated that the responses in both groups were significant, but the response in the stem cell group was significantly lower compared with the standard surgery group. No considerable complications were observed in the two groups.

Conclusion: Although the periurethral injection of MDSCs considerably improves the symptoms with minimum complications in women with SUI, its therapeutic response is significantly lower compared with mid-urethral sling surgery.

Introduction: Achillea millefolium is an Iranian herbal medicine with various effects on the human cells. The aim of this study was to investigate the effects of the aqueous extract of Achillea millefolium (AEAM) on the proliferation and differentiation of mesenchymal stem cells (MSCs).

Methods: In this study, bone marrow-MSCs (BM-MSCs) were obtained from Wister rat bone morrow and then cultured in Dulbecco's modified Eagle's medium /Nutrient Ham's Mixture F-12 (DMEM/F12) media. Then, the isolated MSCs were cultured in either osteocyte or adipocyte differentiation media containing 0.2 or 2 mg/mL AEAM and assessed using specific staining method.

Results: The isolated BM-MSCs exhibited fibroblast-like morphology and were positive for CD73, and CD90, while negative for CD34 and CD45. AEAM significantly increased self-renewal of BM-MSCs at low dose (0.2 mg/ml, P= 0.001) and increased the pool stem cells in both osteocyte and adipocyte differentiation media.

Conclusion: AEAM at low doses may be used in cases where there is a need for large number of stem cells, via increased numbers of MSCs, and help tissue repair and immunomodulation.

Few studies are conducted on the efficacy of human adipose-derived stem cells (ADSCs) in spinal cord injury (SCI) management and electrophysiological changes in the spinal cord. Therefore, the present study aimed to determine the effect of ADSCs on neuropathic pain, motor function recovery, and electrophysiology assessment. For the purpose of this study, adult male Wistar rats (weight: 140-160 gr, n = 42) were randomly allocated into five groups namely intact animals, sham-operated, SCI non-treated animals, vehicle-treated (culture media), and ADSCs treated groups. One week after clips compression SCI induction, about 1×10⁶ cells were transplanted into the spinal cord. As well, both neuropathic pain (allodynia and hyperalgesia) and motor function were measured weekly. Cavity size, ADSCs survival, and electrophysiology assessments were measured at the end of the eighth week. The transplantation of ADSCs resulted in a significant improvement in the locomotion of SCI animals (p<0.0001), mechanical allodynia (p<0.0001), cold allodynia (p<0.0001), mechanical hyperalgesia (p<0.0001), and thermal hyperalgesia (p<0.0001). The cavity size was significantly smaller among the ADSCs-treated animals (p <0.0001). The single-unit recording showed that the transplantation of ADSCs decreased wide dynamic range (WDR) in neurons and it evoked potential in response to receiving signals from Aβ (p<0.0001) and Aδ (p=0.003) C-fiber (p<0.0001) neurons. Post-discharge recorded from WDR neurons decreased after the transplantation of ADSCs (p<0.0001) and wind up in the ADSCs-treated group was lower than that of the SCI group (p=0.003). Our results showed that the transplantation of ADSCs could significantly alleviate neuropathic pain, enhance motor function recovery, and improve electrophysiology findings after SCI.

Eugenol, as the main component in clove, has neuroprotective abilities, including its effect to learning memory of mice. However, there is no evidence showing whether eugenol can expand the growth of dendrites in the brain. The objective of this research was to examine the effects of eugenol towards dendritic complexity of neurons, neurogenesis, and memory performance in hippocampus. A total of 21 mice were divided into three groups; (i) mice were administered 30 mg/kg bw eugenol orally, (ii) mice were administered 100 mg/kg bw eugenol orally, and (iii) mice were administered distilled water as control. Mice were kept for 30 consecutive days following the standard animal housing. The memory performance was observed through the Y-arm maze alternation, Novel Object Recognition (NOR), and Morris Water Maze (MWM) test. The brain was dissected and stained with FD Rapid Golgi StainingTM kit to observe dendrites in the dentate gyrus (DG) and cornu ammonis 1 (CA1) region; and Haematoxylin-Eosin (HE) staining to assess neurogenesis in the DG. Our results showed that eugenol enhanced putative neural stem cells (NPCs) and granular cells (GC) number, and also decrease neuronal cell death in DG (p<0.0001). Eugenol also increased dendritic complexity of neurons in DG region; while in CA1, eugenol has given a positive effect only on the basal area. Eugenol increased spatial and recognition memory in mice, indicated by a higher number of correct alternations and discrimination ratio compared to the control group (p<0.05), although escape latency in MWM did not show significant effect (p>0.05). As analyzed by behavioral tests and Golgi staining of brain tissue, eugenol can increase memory performance, neurogenesis, and dendritic complexity of neurons in the DG and CA1 basal region of brain in mice.

Purpose: To isolate and characterize mesenchymal stem cells of dental follicle from fresh and cryopreserved samples and to test any significant difference in their osteogenic differentiation potential by using digital imaging software. We also investigated whether the cryoprotectant used and its concentration is able to maintain cell count and viability. Methods: Mesenchymal stem cells (MSCs) were isolated from dental follicle of impacted third molars. The osteogenic differentiation potential of dental follicle stem cells was assessed using alizarin red and alkaline phosphatase staining followed by digital imaging quantification of the stains. Results: Dental follicle cells have shown typical characterisation by exhibiting the stem cell stromal markers and hematopoietic markers, but there was variance in the percentage of expression in fresh and cryopreserved samples. There was considerable osteogenic differentiation potential in the fresh sample compared to cryopreserved sample. The cell count and viability were preserved in both samples. Conclusions: The results in the study have shown wide variation of osteogenic differentiation potential in fresh and cryopreserved samples. Also, the cryoprotectant was found to be effective in its purpose at the specified concentration.

Rationale: Cardiac sympathetic nerves are required for endogenous repair of the mammalian neonatal heart in vivo, but the underlying mechanism is unclear. Objective: We tested the hypothesis that a combination of cardiac developmental growth factors Wnt3a, BMP4 and Neuregulin (NRG-1), compensate for denervation and support cardiac regeneration in explanted neonatal mammalian hearts. Methods and Results: Hearts from 2-day old neonatal mice were harvested, lesioned at the apex and grown ex vivo for 21 days under defined conditions. Hearts grown in canonical cardiomyocyte culture media underwent complete coagulative necrosis, a process resembling ischemic cell death, by day 14. However, the addition of Wnt3a, BMP-4 and NRG-1, maintained cellular integrity and restored the endogenous regenerative program. None of these factors alone, or in any paired combination, were sufficient to induce regeneration in culture. rNRG-1 alone significantly reduced the accumulation of double strand DNA damage at Day 3; (-NRG-1: 60±12%; +NRG-1: 8±3%; P<0.01) and prevented coagulative necrosis at Day 14. Short-term addition of rWnt3a and rBMP-4 (day 0-3, NRG-1+) increased WT1 expression (a marker of epicardial cells) 7-fold, epicardial proliferation (78±17 cells vs. 21±9 cells; P<0.05), migration and recellularization (80±22 vs. zero cells; P<0.01; n=6) at the injury site on day 14. Conclusions: A novel explant culture system maintains three-dimensional neonatal mouse hearts and the mammalian neonatal cardiac regenerative program ex vivo. We identified that rNRG-1, plus short-term activation of Wnt- and BMP-signaling, promotes cardiac repair via epicardial cell activation, their proliferation and migration to the injury site, followed by putative cardiomyocyte recruitment. This novel technique will facilitate future studies of mammalian cardiac regeneration and may be useful in cardiac-specific drug testing.

Background: Osteoarthritis is most prevalent in the knee and drives the growing incidence of total knee arthroplasty. There is a need to explore non-surgical treatment options to increase the portfolio of alternatives available. The study aimed to determine the clinical response to an autologous bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) intra-articular injection compared to an active comparator. Methods: The study was a prospective, single-blinded, randomized controlled pilot study. Participants with diagnosed knee osteoarthritis were allocated to one of two treatment groups to receive a BMAC injection immediately followed by a PRP injection or a single injection of Gel-One® crosslinked hyaluronate (HA). Outcomes were assessed at 3, 6, and 12 months post-treatment. Results: Significant improvements were observed in both treatment groups for all Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales with the exception of the symptoms assessment at 12 months in the HA group. BMAC KOOS scores peaked at 12 months, while HA KOOS scores generally peaked at 6 months. The gap in mean scores at 12 months in favor of the BMAC group did not reach statistical significance. Secondary outcomes included a greater reduction in pain at 12 months in the BMAC group (-3.13 points; 95% CI: -3.96, -3.29) compared to the HA group (-1.56 points; 95% CI: -2.59, -0.53; p= 0.02) via the numeric pain rating scale. Conclusions: Results demonstrate that both treatment groups experienced clinically and statistically significant improvement across the KOOS subscales. While BMAC has shown promise in the treatment of knee OA, there is a need for multi-center investigations with larger sample sizes, an extended follow-up, and placebo-based control. ClinicalTrials.gov Identifier: NCT02958267.

It is nowadays taken granted that induced pluripotent stem cells (iPSCs) are available for the regeneration therapy since iPSCs differentiate into any kind of phenotypes. If iPSCs can choose their fate in every way of differentiation why they do not choose cancer phenotype. As a body develops for one fertilized egg, embryonic stem cell must choose every phenotype of tissues such as blood, neuron, lung, liver, pancreas and so on depending on the stages. And sometimes the cells get cancer. So do iPSCs because iPSCs are almost equivalent to embryonic cells. Then how can the safety of the regeneration therapy be maintained with iPSCs? When inducing the differentiation of iPSCs it is considered important to choose the proper conditions of culture such as 3D-platform for embryoid, supplement of cytokines and growth factors, inhibition of signaling and so on. On the other hand, several conditions have been reported to induce cancer stem cells. The cancer inducing conditions are possibly summarized as the factors chronically exposed to iPSCs. It is further worthwhile noticing that the conditions do not appear to induce mutations but affecting the epigenetics. Collectively, to secure the safety of regeneration therapy, it appears the best way to avoid the conditions to induce cancer stem cells. Further insights in details will be discussed in the lecture. Type 1 Diabetes (T1D) is an autoimmune disease characterized by destruction of the pancreatic beta cells and loss of insulin. Using the Edmonton protocol, donor-derived islets seeded into the liver successfully restore glycemia in 58% of T1D patients. However, donor scarcity, risks associated with immunosuppressants and poor engraftment limit this therapeutic application to a small number of patients. To overcome these challenges, the developmental potential of human embryonic stem cells and human induced pluripotent stem cells is being harnessed to produce surrogate islets in vitro. We and others have been able to mimic human embryonic development and generate pancreatic progenitors (PP) that have the ability to mature into insulin-producing beta-like cells both in vitro and in vivo. Transplantation of pancreatic progenitors in the kidney capsule of immunodeficient mice leads to formation of islet-like structures that secrete human insulin. However, there are some limitations to the use of pancreatic progenitors for the treatment of T1D. First and foremost, their safety as the PP population can be heterogenous and highly proliferative, which might lead to formation of cellular outgrowth or teratoma after transplantation. Second, while insulin-producing cells develop in vivo 6 weeks after transplantation, restoration of normoglycemia occurs ~5 months later, suggesting that these "early" insulin-producing cells are immature, or poorly connected to the host vasculature. We have been addressing these two limitations and developed approaches to 1) improve safety by identifying markers to purify the PP