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Stem Cells Translational Medicine

Jun-Nan Tang, Jhon Cores, Ke Huang, Xiao-Lin Cui, Lan Luo, Jin-Ying Zhang, Tao-Sheng Li, Li Qian, Ke Cheng
Stem cell therapy is a promising strategy for tissue regeneration. The therapeutic benefits of cell therapy are mediated by both direct and indirect mechanisms. However, the application of stem cell therapy in the clinic is hampered by several limitations. This concise review provides a brief introduction into stem cell therapies for ischemic heart disease. It summarizes cell-based and cell-free paradigms, their limitations, and the benefits of using them to target disease. Stem Cells Translational Medicine 2018...
February 22, 2018: Stem Cells Translational Medicine
David M Burmeister, Randolph Stone, Nicole Wrice, Alfred Laborde, Sandra C Becerra, Shanmugasundaram Natesan, Robert J Christy
Harvesting of autografts results in donor site morbidities and is limited in scenarios such as large total body surface area burns. In these instances, coverage is increased by meshing grafts at the expense of delayed biologic closure. Moreover, graft meshing increases the likelihood of contraction and hypertrophic scarring, limits range of motion, and worsens cosmesis. Many tissue engineering technologies have touted the promise of adipose-derived stem cells (ASCs) for burn wounds. The primary objective of the current study was to determine feasibility and efficacy of in situ ASC delivery via PEGylated fibrin (FPEG) hydrogels as adjuncts to meshed split thickness skin grafts in a porcine model...
February 18, 2018: Stem Cells Translational Medicine
Xiangyu Zou, Kai Jiang, Amrutesh S Puranik, Kyra L Jordan, Hui Tang, Xiangyang Zhu, Lilach O Lerman
Mesenchymal stem cells (MSC) have been experimentally used for kidney repair, but modest retention limits their efficacy. Cell-surface coating allows modulating MSC homing and interaction with target cells. We coated mouse adipose tissue-derived MSC with antibodies directed against kidney injury molecule-1 (ab-KIM1), which is upregulated in injured kidneys, and tested the hypothesis that this would enhance their therapeutic effects in ischemic kidney injury. Untreated MSC, ab-KIM1-coated MSC (KIM-MSC), or vehicle, were injected systemically into the carotid artery of 2-kidneys, 1-clip mice 2 weeks after surgery...
February 15, 2018: Stem Cells Translational Medicine
Alessia Brossa, Elli Papadimitriou, Federica Collino, Danny Incarnato, Salvatore Oliviero, Giovanni Camussi, Benedetta Bussolati
Renal repair after injury is dependent on clonal expansion of proliferation-competent cells. In the human kidney, the expression of CD133 characterizes a population of resident scattered cells with resistance to damage and ability to proliferate. However, the biological function of the CD133 molecule is unknown. By RNA sequencing, we found that cells undergoing cisplatin damage lost the CD133 signature and acquired metanephric mesenchymal and regenerative genes such as SNAIL1, KLF4, SOX9, and WNT3. CD133 was reacquired in the recovery phase...
February 12, 2018: Stem Cells Translational Medicine
Elena Arrigoni, Marzia Del Re, Sara Galimberti, Giuliana Restante, Eleonora Rofi, Stefania Crucitta, Claudia Baratè, Mario Petrini, Romano Danesi, Antonello Di Paolo
Nowadays, more than 90% of patients affected by chronic myeloid leukemia (CML) survive with a good quality of life, thanks to the clinical efficacy of tyrosine kinase inhibitors (TKIs). Nevertheless, point mutations of the ABL1 pocket occurring during treatment may reduce binding of TKIs, being responsible of about 20% of cases of resistance among CML patients. In addition, the presence of leukemic stem cells (LSCs) represents the most important event in leukemia progression related to TKI resistance. LSCs express stem cell markers, including active efflux pumps and genetic and epigenetic alterations together with deregulated cell signaling pathways involved in self-renewal, such as Wnt/β-catenin, Notch, and Hedgehog...
February 8, 2018: Stem Cells Translational Medicine
Michael Chez, Christopher Lepage, Carol Parise, Ashley Dang-Chu, Andrea Hankins, Michael Carroll
The aim of this exploratory study was to assess the safety and clinical effects of autologous umbilical cord blood (AUCB) infusion in children with idiopathic autism spectrum disorder (ASD). Twenty-nine children 2 to 6 years of age with a confirmed diagnosis of ASD participated in this randomized, blinded, placebo-controlled, crossover trial. Participants were randomized to receive AUCB or placebo, evaluated at baseline, 12, and 24 weeks, received the opposite infusion, then re-evaluated at the same time points...
February 6, 2018: Stem Cells Translational Medicine
Bret H Clough, Suzanne Zeitouni, Ulf Krause, Christopher D Chaput, Lauren M Cross, Akhilesh K Gaharwar, Carl A Gregory
Non-union defects of bone are a major problem in orthopedics, especially for patients with a low healing capacity. Fixation devices and osteoconductive materials are used to provide a stable environment for osteogenesis and an osteogenic component such as autologous human bone marrow (hBM) is then used, but robust bone formation is contingent on the healing capacity of the patients. A safe and rapid procedure for improvement of the osteoanabolic properties of hBM is, therefore, sought after in the field of orthopedics, especially if it can be performed within the temporal limitations of the surgical procedure, with minimal manipulation, and at point-of-care...
February 5, 2018: Stem Cells Translational Medicine
Connor P Dolan, Lindsay A Dawson, Ken Muneoka
Regeneration Biology is the study of organisms with endogenous regenerative abilities, whereas Regenerative Medicine focuses on engineering solutions for human injuries that do not regenerate. While the two fields are fundamentally different in their approach, there is an obvious interface involving mammalian regeneration models. The fingertip is the only part of the human limb that is regeneration-competent and the regenerating mouse digit tip has emerged as a model to study a clinically relevant regenerative response...
February 5, 2018: Stem Cells Translational Medicine
Sudipto Bari, Qixing Zhong, Xiubo Fan, Zhiyong Poon, Alvin Soon Tiong Lim, Tse Hui Lim, Niraja Dighe, Shang Li, Gigi Ngar Chee Chiu, Christina Li Lin Chai, William Ying Khee Hwang
Umbilical cord blood (UCB) transplants in adults have slower hematopoietic recovery compared to bone marrow (BM) or peripheral blood (PB) stem cells mainly due to low number of total nucleated cells and hematopoietic stem and progenitor cells (HSPC). As such in this study, we aimed to perform ex vivo expansion of UCB HSPC from non-enriched mononucleated cells (MNC) using novel azole-based small molecules. Freshly-thawed UCB-MNC were cultured in expansion medium supplemented with small molecules and basal cytokine cocktail...
February 2, 2018: Stem Cells Translational Medicine
Kirsi Kuismanen, Miia Juntunen, Nathaniel Narra Girish, Heikki Tuominen, Heini Huhtala, Kari Nieminen, Jari Hyttinen, Susanna Miettinen
Anal incontinence is a devastating condition that significantly reduces the quality of life. Our aim was to evaluate the effect of human adipose stem cell (hASC) injections in a rat model for anal sphincter injury, which is the main cause of anal incontinence in humans. Furthermore, we tested if the efficacy of hASCs could be improved by combining them with polyacrylamide hydrogel carrier, Bulkamid®. Human ASCs derived from a female donor were culture expanded in DMEM/F12 supplemented with human platelet lysate...
January 31, 2018: Stem Cells Translational Medicine
Jean L Tan, Sin N Lau, Bryan Leaw, Hong P T Nguyen, Lois A Salamonsen, Mohamed I Saad, Siow T Chan, Dandan Zhu, Mirja Krause, Carla Kim, William Sievert, Euan M Wallace, Rebecca Lim
Idiopathic pulmonary fibrosis (IPF) is characterized by chronic inflammation, severe scarring, and stem cell senescence. Stem cell-based therapies modulate inflammatory and fibrogenic pathways by release of soluble factors. Stem cell-derived extracellular vesicles should be explored as a potential therapy for IPF. Human amnion epithelial cell-derived exosomes (hAEC Exo) were isolated and compared against human lung fibroblasts exosomes. hAEC Exo were assessed as a potential therapy for lung fibrosis. Exosomes were isolated and evaluated for their protein and miRNA cargo...
January 3, 2018: Stem Cells Translational Medicine
Rebekah M Samsonraj, Amel Dudakovic, Bushra Manzar, Buer Sen, Allan B Dietz, Simon M Cool, Janet Rubin, Andre J van Wijnen
Strategies for musculoskeletal tissue regeneration apply adult mesenchymal stem/stromal cells (MSCs) that can be sourced from bone marrow- and lipo-aspirates. Adipose tissue-derived MSCs are more easily harvested in the large quantities required for skeletal tissue-engineering approaches, but are generally considered to be less osteogenic than bone marrow MSCs. Therefore, we tested a new molecular strategy to improve their osteogenic lineage-differentiation potential using the fungal metabolite cytochalasin D (CytoD)...
December 27, 2017: Stem Cells Translational Medicine
Yasuo Morishima, Fumihiro Azuma, Koichi Kashiwase, Kayoko Matsumoto, Takeshi Orihara, Hiromasa Yabe, Shunichi Kato, Koji Kato, Shunro Kai, Tetsuo Mori, Kazunori Nakajima, Satoko Morishima, Masahiro Satake, Minoko Takanashi, Toshio Yabe
Clinical application of induced pluripotent stem cells (iPS) in autologous settings has just begun. To overcome the high time and cost barriers in the individual production of autologous iPS, the use of allogeneic iPS with a homozygous human leukocyte antigen (HLA) haplotype (HLA-homo HP) has been proposed. Cord blood transplantation (CBT) is a suitable model for evaluating the allogeneic immunogenicity of iPS transplantation from HLA-homo donors. We analyzed 1,374 Japanese single cord blood transplant pairs who were retrospectively typed as HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1...
December 23, 2017: Stem Cells Translational Medicine
Jennifer Simkin, Ashley W Seifert
Despite approaches in regenerative medicine using stem cells, bio-engineered scaffolds, and targeted drug delivery to enhance human tissue repair, clinicians remain unable to regenerate large-scale, multi-tissue defects in situ. The study of regenerative biology using mammalian models of complex tissue regeneration offers an opportunity to discover key factors that stimulate a regenerative rather than fibrotic response to injury. For example, although primates and rodents can regenerate their distal digit tips, they heal more proximal amputations with scar tissue...
December 22, 2017: Stem Cells Translational Medicine
Jana Karbanová, Aurelio Lorico, Martin Bornhäuser, Denis Corbeil, Christine A Fargeas
The cell surface antigen prominin-1 (alias CD133) has gained enormous interest in the last two decades and given rise to debates as to its utility as a biological stem and cancer stem cell marker. Important and yet often overlooked knowledge that is pertinent to its physiological function has been generated in other systems given its more general expression beyond primitive cells. This article briefly discusses the importance of particular biochemical features of CD133 with relation to its association with membrane microdomains (lipid rafts) and proper immunodetection...
December 22, 2017: Stem Cells Translational Medicine
Jie Zhu, Joseph Reynolds, Thelma Garcia, Helen Cifuentes, Shereen Chew, Xianmin Zeng, Deepak Ashok Lamba
Retinal degeneration often results in the loss of light-sensing photoreceptors, which leads to permanent vision loss. Generating transplantable retinal photoreceptors using human somatic cell-derived induced pluripotent stem cells (iPSCs) holds promise to treat a variety of retinal degenerative diseases by replacing the damaged or dysfunctional native photoreceptors with healthy and functional ones. Establishment of effective methods to produce retinal cells including photoreceptors in chemically defined conditions using current Good Manufacture Practice (cGMP)-manufactured human iPSC lines is critical for advancing cell replacement therapy to the clinic...
December 21, 2017: Stem Cells Translational Medicine
Olga Milczarek, Danuta Jarocha, Anna Starowicz-Filip, Stanislaw Kwiatkowski, Bogna Badyra, Marcin Majka
There is a need among patients suffering from drug-resistant epilepsy (DRE) for more efficient and less toxic treatments. The objective of the present study was to assess the safety, feasibility, and potential efficacy of autologous bone marrow cell transplantation in pediatric patients with DRE. Two females and two males (11 months to 6 years) were enrolled and underwent a combined therapy consisting of autologous bone marrow nucleated cells (BMNCs) transplantation (intrathecal: 0.5 × 109 ; intravenous: 0...
December 10, 2017: Stem Cells Translational Medicine
Anastasia Brooks, Kathryn Futrega, Xiaowen Liang, Xiaoling Hu, Xin Liu, Darrell H G Crawford, Michael R Doran, Michael S Roberts, Haolu Wang
Mesenchymal stem/stromal cells (MSCs) present a promising tool in cell-based therapy for treatment of various diseases. Currently, optimization of treatment protocols in clinical studies is complicated by the variations in cell dosing, diverse methods used to deliver MSCs, and the variety of methods used for tracking MSCs in vivo. Most studies use a dose escalation approach, and attempt to correlate efficacy with total cell dose. Optimization could be accelerated through specific understanding of MSC distribution in vivo, long-term viability, as well as their biological fate...
December 6, 2017: Stem Cells Translational Medicine
Sang Jin Lee, Hung-Jen Wang, Tae-Hyoung Kim, Jin San Choi, Gauri Kulkarni, John D Jackson, Anthony Atala, James J Yoo
Host stem/progenitor cells can be mobilized and recruited to a target location using biomaterials, and these cells may be used for in situ tissue regeneration. The objective of this study was to investigate whether host biologic resources could be used to regenerate renal tissue in situ. Collagen hydrogel was injected into the kidneys of normal mice, and rat kidneys that had sustained ischemia/reperfusion injury. After injection, the kidneys of both animal models were examined up to 4 weeks for host tissue response...
February 2018: Stem Cells Translational Medicine
Sabina Frljak, Martina Jaklic, Gregor Zemljic, Andraz Cerar, Gregor Poglajen, Bojan Vrtovec
We investigated the effects of CD34+cell therapy on right ventricular (RV) function in patients with nonischemic dilated cardiomyopathy (DCM). We enrolled 60 patients with DCM who were randomized to CD34+cell therapy (Stem Cells (SC) Group n = 30), or no cell therapy (Controls, n = 30). The SC Group received granulocyte-colony stimulating factor, and CD34+cells were collected by apheresis and injected transendocardially. Patients were followed for 6 months. At baseline, the groups did not differ in age, gender, left ventricular ejection fraction, N-terminal probrain natriuretic peptide, or parameters of RV function...
February 2018: Stem Cells Translational Medicine
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