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Stem Cells Translational Medicine

Shih-Yin Chen, Meng-Chieh Lin, Jia-Shiuan Tsai, Pei-Lin He, Wen-Ting Luo, Harvey Herschman, Hua-Jung Li
Adult brains have limited regenerative capacity. Consequently, both brain damage and neurodegenerative diseases often cause functional impairment for patients. Mesenchymal stem cells (MSCs), one type of adult stem cells, can be isolated from various adult tissues. MSCs have been used in clinical trials to treat human diseases and the therapeutic potentials of the MSC-derived secretome and extracellular vesicles (EVs) have been under investigation. We found that blocking the prostaglandin E2 /prostaglandin E2 receptor 4 (PGE2 /EP4 ) signaling pathway in MSCs with EP4 antagonists increased EV release and promoted the sorting of specific proteins, including anti-inflammatory cytokines and factors that modify astrocyte function, blood-brain barrier integrity, and microglial migration into the damaged hippocampus, into the EVs...
March 19, 2019: Stem Cells Translational Medicine
Zohreh Sadat Badieyan, Todd Evans
Chemically modified RNA (cmRNA) has potential as a safe and efficient tool for nucleic acid-based therapies and regenerative medicine. Modifications in the chemistry of mRNA can enhance stability, reduce immunogenicity, and thus facilitate mRNA-based nucleic acid therapy, which eliminates risk of insertional mutagenesis. In addition to these valuable advantages, the mRNA-based method showed significantly higher efficacy for reprogramming somatic cells to pluripotency compared with DNA- or protein-based methods...
March 19, 2019: Stem Cells Translational Medicine
Yasuyoshi Kimura, Tomoko Shofuda, Yuichiro Higuchi, Ippei Nagamori, Masaaki Oda, Masayuki Nakamori, Masafumi Onodera, Daisuke Kanematsu, Atsuyo Yamamoto, Asako Katsuma, Hiroshi Suemizu, Toru Nakano, Yonehiro Kanemura, Hideki Mochizuki
The use of human induced pluripotent stem cells (hiPSCs) and recent advances in cell engineering have opened new prospects for cell-based therapy. However, there are concerns that must be addressed prior to their broad clinical applications and a major concern is tumorigenicity. Suicide gene approaches could eliminate wayward tumor-initiating cells even after cell transplantation, but their efficacy remains controversial. Another concern is the safety of genome editing. Our knowledge of human genomic safe harbors (GSHs) is still insufficient, making it difficult to predict the influence of gene integration on nearby genes...
March 19, 2019: Stem Cells Translational Medicine
Laura Simons, Marina Cavazzana, Isabelle André
Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for a large number of malignant and nonmalignant (inherited) diseases of the hematopoietic system. Nevertheless, non-HLA identical transplantations are complicated by a severe T cell immunodeficiency associated with a high rate of infection, relapse and graft-versus-host disease. Initial recovery of T cell immunity following HSCT relies on peripheral expansion of memory T cells mostly driven by cytokines. The reconstitution of a diverse, self-tolerant, and naive T cell repertoire, however, may take up to 2 years and crucially relies on the interaction of T cell progenitors with the host thymic epithelium, which may be altered by GvHD, age or transplant-related toxicities...
March 18, 2019: Stem Cells Translational Medicine
Francisco Bandeira, Gary Hin-Fai Yam, Matthias Fuest, Hon Shing Ong, Yu-Chi Liu, Xin-Yi Seah, S Y Shen, Jodhbir S Mehta
The conjunctiva is a clear tissue covering the white part of the eye and lines the back of the eyelids. Conjunctival diseases, such as symblepharon, cause inflammation, discharges, and photophobia. The treatment often requires excision of large parts of conjunctiva. Tissue engineering of conjunctival cells using human amniotic membrane (HAM) denuded of its epithelium as a basement membrane scaffold has been shown to be effective for covering conjunctival defects. However, most epithelial denudation protocols are time-consuming and expensive or compromise HAM's basement membrane structure and matrix components...
March 13, 2019: Stem Cells Translational Medicine
Andres F Martinez, William M Miller
Patients suffering from acute or sustained thrombocytopenia require platelet transfusions, which are entirely donor-based and limited by challenges related to storage and fluctuating supply. Developing cell-culture technologies will enable ex vivo and donor-independent platelet production. However, critical advancements are needed to improve scalability and increase megakaryocyte (Mk) culture productivity. To address these needs, we evaluated Mk production from mobilized peripheral blood CD34+ cells cultured on a commercially available gas-permeable silicone rubber membrane, which provides efficient gas exchange, and investigated the use of fed-batch media dilution schemes...
March 8, 2019: Stem Cells Translational Medicine
Hal E Broxmeyer
No abstract text is available yet for this article.
March 7, 2019: Stem Cells Translational Medicine
(no author information available yet)
No abstract text is available yet for this article.
March 7, 2019: Stem Cells Translational Medicine
Woo-Suk Lee, Hwan Jin Kim, Kang-Il Kim, Gi Beom Kim, Wook Jin
Mesenchymal stem cells (MSCs) have been the focus of an emerging treatment for osteoarthritis. However, few studies reported about outcomes of an intra-articular injection of autologous adipose-derived mesenchymal stem cells (AD-MSCs). This study aimed to assess the efficacy and safety of a single intra-articular injection of AD-MSCs for patients with knee osteoarthritis. It was a prospective double-blinded, randomized controlled, phase IIb clinical trial. AD-MSCs were administered for 12 patients (MSC group), and the group was compared with 12 knees with injection of normal saline (control group) up to 6 months...
March 5, 2019: Stem Cells Translational Medicine
Xiang Xue, Yan Yan, Ye Ma, Yang Yuan, Chunguang Li, Xilong Lang, Zhiyun Xu, Hezhong Chen, Hao Zhang
Esophageal anastomotic leakage (EAL) is a devastating complication for esophagectomy but the available therapies are unsatisfactory. Due to the healing effects of mesenchymal stromal cells (MSCs) and supporting capability of fibrin scaffold (FS), we evaluated the efficacy of a stem-cell therapy for EAL by engrafting adult and autologous MSCs (AAMSCs) in FS and investigated the potential mechanism. Twenty-one rabbits were assigned to AAMSC/FS group (n = 12) and control group (n = 9). After harvested, AAMSCs were identified and then labeled with lenti...
February 27, 2019: Stem Cells Translational Medicine
Yu Zhu, Yachao Jia, Yanmao Wang, Jia Xu, Yimin Chai
Stem cell-derived exosomes have exhibited promise for applications in tissue regeneration. However, one major problem for stem cell-derived exosome therapies is identifying appropriate source cells. In the present study, we aimed to compare the bone regenerative effect of exosomes secreted by bone marrow mesenchymal stem cells (BMSCs) derived from type 1 diabetes rats (dBMSC-exos) and exosomes secreted by BMSCs derived from normal rats (nBMSC-exos). BMSCs were isolated from rats with streptozotocin-induced diabetes and normal rats...
February 26, 2019: Stem Cells Translational Medicine
Monika Řehořová, Ingrid Vargová, Serhiy Forostyak, Irena Vacková, Karolína Turnovcová, Helena Kupcová Skalníková, Petr Vodička, Šárka Kubinová, Eva Syková, Pavla Jendelová
An increasing number of studies have demonstrated the beneficial effects of human mesenchymal stem cells (hMSC) in the treatment of amyotrophic lateral sclerosis (ALS). We compared the effect of repeated intrathecal applications of hMSC or their conditioned medium (CondM) using lumbar puncture or injection into the muscle (quadriceps femoris), or a combination of both applications in symptomatic SOD1G93A rats. We further assessed the effect of the treatment on three major cell death pathways (necroptosis, apoptosis, and autophagy) in the spinal cord tissue...
February 25, 2019: Stem Cells Translational Medicine
Lisa R Trump, Ramesh C Nayak, Abhishek K Singh, Sana Emberesh, Ashley M Wellendorf, Carolyn M Lutzko, Jose A Cancelas
Bacterial and fungal infections are a major cause of morbidity and mortality in neutropenic patients. Donor derived neutrophil transfusions have been used for prophylaxis or treatment for infection in neutropenic patients. However, the short half-life and the limited availability of large numbers of donor derived neutrophils for transfusion remain a significant hurdle in the implementation of neutrophil transfusion therapy. Here, we investigate the in vitro and in vivo activity of neutrophils generated from human induced pluripotent stem cells (iPSC), a potentially unlimited resource to produce neutrophils for transfusion...
February 21, 2019: Stem Cells Translational Medicine
Chun S Park, Andrew Lewis, Taylor Chen, Daniel Lacorazza
Pluripotent and tissue-specific stem cells, such as blood-forming stem cells, are maintained through a balance of quiescence, self-renewal, and differentiation. Self-renewal is a specialized cell division that generates daughter cells with the same features as the parental stem cell. Although many factors are involved in the regulation of self-renewal, perhaps the most well-known factors are members of the Krüppel-like factor (KLF) family, especially KLF4, because of the landmark discovery that this protein is required to reprogram somatic cells into induced pluripotent stem cells...
February 21, 2019: Stem Cells Translational Medicine
Jesse F Wang, Ming-Song Lee, Tsung-Lin Tsai, Ellen M Leiferman, Darrin J Trask, Matthew W Squire, Wan-Ju Li
Patients with type 1 diabetes mellitus (T1DM) often suffer from osteopenia or osteoporosis. Although most agree that T1DM-induced hyperglycemia is a risk factor for progressive bone loss, the mechanisms for the link between T1DM and bone loss still remain elusive. In this study, we found that bone marrow-derived mesenchymal stem cells (BMSCs) isolated from T1DM donors were less inducible for osteogenesis than those from non-T1DM donors and further identified a mechanism involving bone morphogenetic protein-6 (BMP6) that was produced significantly less in BMSCs derived from T1DM donors than that in control cells...
February 19, 2019: Stem Cells Translational Medicine
Tao Lv, Yunpeng Gu, Jianhai Bi, Ning Kang, Zhigang Yang, Xin Fu, Qian Wang, Li Yan, Xia Liu, Yilin Cao, Ran Xiao
Fat grafting procedures are considered to be a promising regenerative, cell-directed therapy; however, their survival is mainly influenced by ischemia condition. Fructose 1,6-bisphosphate (FBP), as an intermediate in energy metabolism, has the potential to rescue cells and tissues from hypoxic-ischemic circumstances. In the present study, human lipoaspirates were grafted subcutaneously into nude mice followed by a daily intraperitoneal injection of FBP at different doses for 7 days. Next, the grafts were harvested at different time points till 12 weeks postimplantation and were evaluated for cell viability and function, tissue revascularization and inflammatory cell infiltration using histological analysis, whole-mount living tissue imaging, glycerol 3-phosphate dehydrogenase activity assays, and quantitative analysis of gene expression...
February 18, 2019: Stem Cells Translational Medicine
Jarel K Gandhi, Travis Knudsen, Matthew Hill, Bhaskar Roy, Lori Bachman, Cynthia Pfannkoch-Andrews, Karina N Schmidt, Muriel M Metko, Michael J Ackerman, Zachary Resch, Jose S Pulido, Alan D Marmorstein
Human fibrin hydrogels are a popular choice for use as a biomaterial within tissue engineered constructs because they are biocompatible, nonxenogenic, autologous use compatible, and biodegradable. We have recently demonstrated the ability to culture induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium on fibrin hydrogels. However, iPSCs themselves have relatively few substrate options (e.g., laminin) for expansion in adherent cell culture for use in cell therapy. To address this, we investigated the potential of culturing iPSCs on fibrin hydrogels for three-dimensional applications and further examined the use of fibrinogen, the soluble precursor protein, as a coating substrate for traditional adherent cell culture...
February 15, 2019: Stem Cells Translational Medicine
Sergei A Kuznetsov, Astar Hailu-Lazmi, Natasha Cherman, Luis F de Castro, Pamela G Robey, Raphael Gorodetsky
Osteoarthritic and other types of articular cartilage defects never heal on their own. Medicinal and surgical approaches are often ineffective, and the supply of autologous chondrocytes for tissue engineering is very limited. Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) have been suggested as an adequate cell source for cartilage reconstruction. However, the majority of studies employing BMSCs for cartilage tissue engineering have used BMSCs predifferentiated into cartilage prior to implantation...
February 14, 2019: Stem Cells Translational Medicine
Marco Zarbin, Ilene Sugino, Ellen Townes-Anderson
Retinal cell therapy can have the objectives of rescue (i.e., modulation of metabolic abnormalities primarily for sight preservation) as well as replacement (i.e., replace cells lost due to injury or disease for sight restoration as well as preservation). The first clinical trials of retinal pigment epithelium (RPE) transplantation for vision-threatening complications of age-related macular degeneration (AMD) have begun with some preliminary signs of success (e.g., improvement in vision in some patients, anatomic evidence of transplant-host integration with some evidence of host photoreceptor recovery, long-term survival of autologous induced pluripotent stem cell-derived RPE transplants without immune suppression) as well as limitations (e...
February 12, 2019: Stem Cells Translational Medicine
Michael T Schweizer, Hao Wang, Trinity J Bivalacqua, Alan W Partin, Su Jin Lim, Carolyn Chapman, Rehab Abdallah, Oren Levy, Neil A Bhowmick, Jeffrey M Karp, Angelo De Marzo, John T Isaacs, W Nathaniel Brennen, Samuel R Denmeade
Animal models show that systemically administered bone marrow-derived mesenchymal stem cells (MSCs) home to sites of primary and metastatic prostate cancer (PC)-making them candidates to selectively deliver cytotoxic agents. To further assess this potential as a cell-based therapeutic vehicle, a phase I study testing homing of systemically infused allogeneic MSCs preprostatectomy was conducted. The primary objective was to assess safety and feasibility and to determine if MSCs accumulate within primary PC tissue...
February 8, 2019: Stem Cells Translational Medicine
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