Abstract:
:Cell-based therapy targeting spinal cord injury (SCI) is an attractive approach to promote functional recovery by replacing damaged tissue. We and other groups have reported the effectiveness of transplanting neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) in SCI animal models for neuronal replacement. Glial replacement is an additional approach for tissue repair; however, the lack of robust procedures to drive iPSCs into NS/PCs which can produce glial cells has hindered the development of glial cell transplantation for the restoration of neuronal functions after SCI. Here, we established a method to generate NS/PCs with gliogenic competence (gNS/PCs) optimized for clinical relevance and utilized them as a source of therapeutic NS/PCs for SCI. We could successfully generate gNS/PCs from clinically relevant hiPSCs, which efficiently produced astrocytes and oligodendrocytes in vitro. We also performed comparison between gNS/PCs and neurogenic NS/PCs based on single cell RNA-seq analysis and found that gNS/PCs were distinguished by expression of several transcription factors including HEY2 and NFIB. After gNS/PC transplantation, the graft did not exhibit tumor-like tissue formation, indicating the safety of them as a source of cell therapy. Importantly, the gNS/PCs triggered functional recovery in an SCI animal model, with remyelination of demyelinated axons and improved motor function. Given the inherent safety of gNS/PCs and favorable outcomes observed after their transplantation, cell-based medicine using the gNS/PCs-induction procedure described here together with clinically relevant iPSCs is realistic and would be beneficial for SCI patients.
journal_name
Stem Cells Transl Medjournal_title
Stem cells translational medicineauthors
Kamata Y,Isoda M,Sanosaka T,Shibata R,Ito S,Okubo T,Shinozaki M,Inoue M,Koya I,Shibata S,Shindo T,Matsumoto M,Nakamura M,Okano H,Nagoshi N,Kohyama Jdoi
10.1002/sctm.20-0269subject
Has Abstractpub_date
2020-11-23 00:00:00eissn
2157-6564issn
2157-6580pub_type
杂志文章abstract::To optimize the regenerative proficiency of stem cells, a cardiopoietic protein-based cocktail consisting of multiple growth factors has been developed and advanced into clinical trials for treatment of ischemic heart failure. Streamlining the inductors of cardiopoiesis would address the resource intensive nature of t...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.20-0193
更新日期:2020-10-24 00:00:00
abstract::Repair of injured lungs represents a longstanding therapeutic challenge. We recently demonstrated that human and mouse embryonic lung tissue from the canalicular stage of development are enriched with lung progenitors, and that a single cell suspension of canalicular lungs can be used for transplantation, provided tha...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.17-0149
更新日期:2018-01-01 00:00:00
abstract::An understanding of how cancer cells adapt dormancy would allow for targeted treatment. The current literature suggests that the cancer stem cells might be the major cells with the ability to become quiescent and to resist current drug treatment. The properties of cancer stem cells and healthy stem cells are functiona...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.5966/sctm.2014-0013
更新日期:2014-07-01 00:00:00
abstract::Vascular changes, including blood brain barrier destabilization, are common pathological features in multiple sclerosis (MS) lesions. Blood vessels within adult organs are reported to harbor mesenchymal stromal cells (MSCs) with phenotypical and functional characteristics similar to pericytes. We performed an immunohi...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.17-0028
更新日期:2017-10-01 00:00:00
abstract::Patient-specific induced pluripotent stem cells (iPSCs) hold great promise for studies on disease-related developmental processes and may serve as an autologous cell source for future treatment of many hereditary diseases. New genetic engineering tools such as zinc finger nucleases and transcription activator-like eff...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2013-0017
更新日期:2013-09-01 00:00:00
abstract::Development of efficient and reproducible conditions for directed differentiation of pluripotent stem cells into specific cell types is important not only to understand early human development but also to enable more practical applications, such as in vitro disease modeling, drug discovery, and cell therapies. The dif...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2016-0088
更新日期:2017-02-01 00:00:00
abstract::The specific cell surface markers on mesenchymal stem/progenitor cells (MSCs) have been poorly defined in vivo, but in one recent study, an MSC subpopulation was directly isolated from a CD271-positive fraction of human bone marrow cells. The aim of this study was to identify circulating CD271(+) MSCs in human periphe...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2011-0051
更新日期:2012-06-01 00:00:00
abstract::: Phosphatase and tension homolog (PTEN) is a widely known negative regulator of insulin/phosphatidylinositol 3-kinase (PI3K) signaling. The PI3K/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) and Ras-extracellular signal-regulated kinase (Ras-ERK) signaling pathways are the chief mechanisms controlling the surviva...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0200
更新日期:2016-10-01 00:00:00
abstract:UNLABELLED:Histone deacetylase (HDAC) inhibitors possess therapeutic potential to reverse aberrant epigenetic changes associated with cancers, neurological diseases, and immune disorders. Unfortunately, clinical studies with some HDAC inhibitors displayed delayed cardiac adverse effects, such as atrial fibrillation and...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0279
更新日期:2016-05-01 00:00:00
abstract::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 ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.17-0086
更新日期:2018-02-01 00:00:00
abstract::The method of isolation of bone marrow (BM) mesenchymal stem/stromal cells (MSCs) is a limiting factor in their study and therapeutic use. MSCs are typically expanded from BM cells selected on the basis of their adherence to plastic, which results in a heterogeneous population of cells. Prospective identification of t...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2012-0155
更新日期:2013-08-01 00:00:00
abstract::We conducted a phase II, noncomparative, multicenter study to assess the efficacy and safety of allogeneic bone marrow-derived mesenchymal stromal cells (BM-MSCs) expanded in vitro for patients with aplastic anemia (AA) refractory to immunosuppressive therapy. Seventy-four patients from seven centers received allogene...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,多中心研究
doi:10.1002/sctm.16-0227
更新日期:2017-07-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) can be isolated from bone marrow or other adult tissues (adipose tissue, dental pulp, amniotic fluid, and umbilical cord). In vitro, MSCs grow as adherent cells, display fibroblast-like morphology, and self-renew, undergoing specific mesodermal differentiation. High heterogeneity of MSCs ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.1002/sctm.20-0161
更新日期:2020-11-01 00:00:00
abstract::Mesenchymal stem cells (multipotent stromal cells; MSCs) have been under investigation for the treatment of diverse diseases, with many promising outcomes achieved in animal models and clinical trials. The biological activity of MSC therapies has not been fully resolved which is critical to rationalizing their use and...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.1002/sctm.19-0446
更新日期:2020-09-01 00:00:00
abstract:UNLABELLED:Rotator cuff tendon tear is one of the most common causes of chronic shoulder pain and disability. In this study, we investigated the therapeutic effects of ultrasound-guided human umbilical cord blood (UCB)-derived mesenchymal stem cell (MSC) injection to regenerate a full-thickness subscapularis tendon tea...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0040
更新日期:2015-11-01 00:00:00
abstract::Bone marrow mesenchymal stem cells (BMSCs) have been shown to offer a wide variety of cellular functions including the protective effects on damaged hearts. Here we investigated the antiaging properties of BMSCs and the underlying mechanism in a cellular model of cardiomyocyte senescence and a rat model of aging heart...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2014-0206
更新日期:2015-05-01 00:00:00
abstract::The translation of stem cell-based regenerative solutions from the laboratory to the clinic is often hindered by the culture conditions used to expand cell populations. Although fetal bovine serum (FBS) is widely used, regulatory bodies and safety concerns encourage alternative, xeno-free culturing practices. In an at...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2012-0137
更新日期:2014-02-01 00:00:00
abstract::Infection with the SARS-CoV-2 virus has rapidly become a global pandemic for which we were not prepared. Several clinical trials using previously approved drugs and drug combinations are urgently under way to improve the current situation. A vaccine option has only recently become available, but worldwide distribution...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.20-0181
更新日期:2021-02-01 00:00:00
abstract::Improved therapeutic assessment of experimental traumatic brain injury (TBI), using mesenchymal stem cells (MSCs), would immensely benefit its therapeutic management. Neurometabolite patterns at injury site, measured with proton magnetic resonance spectroscopy (1H-MRS) after MSCs transplantation, may serve as a bio-in...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2016-0087
更新日期:2017-01-01 00:00:00
abstract::Patient-specific induced pluripotent stem cells (iPSCs) hold great promise for many applications, including disease modeling to elucidate mechanisms involved in disease pathogenesis, drug screening, and ultimately regenerative medicine therapies. A frequently used starting source of cells for reprogramming has been de...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2014-0121
更新日期:2014-12-01 00:00:00
abstract:UNLABELLED:The oral cavity possesses a diverse microflora, yet recurrent infections within healthy individuals are rare. Wound healing within the buccal mucosa is preferential, potentially because of the presence of oral mucosal lamina propria-progenitor cells (OMLP-PCs). In addition to their multipotency, OMLP-PCs dem...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0043
更新日期:2015-11-01 00:00:00
abstract:UNLABELLED:Human cord blood (CB)-derived hematopoietic stem cells (HSCs) are an interesting source for HSC transplantation. However, the number of collected CB-HSCs is often too low for one transplantation; therefore, ex vivo expansion of CB-HSCs is desirable. Current expansion protocols are based on the use of cytokin...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2014-0284
更新日期:2015-09-01 00:00:00
abstract::: Liver fibrosis represents the end stage of chronic liver inflammatory diseases and is defined by the abnormal accumulation of extracellular matrix in the liver. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension. Liver transplantation has been the most effective treatment for these ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0343
更新日期:2016-11-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) are very attractive candidates in cell-based strategies that target inflammatory diseases. Preclinical animal studies and many clinical trials have demonstrated that human MSCs can be safely administered and that they modify the inflammatory process in the targeted injured tissue. Our lab...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2012-0025
更新日期:2012-07-01 00:00:00
abstract::The immunomodulatory activity of mesenchymal stem/stromal cells (MSCs) to suppress innate and adaptive immune responses offers a potent cell therapy for modulating inflammation and promoting tissue regeneration. However, the inflammatory cytokine milieu plays a critical role in stimulating MSC immunomodulatory activit...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2016-0044
更新日期:2017-01-01 00:00:00
abstract::Steroid-induced osteonecrosis of the femoral head (ONFH) is characterized by decreased osteogenesis, angiogenesis, and increased adipogenesis. While bone tissue engineering has been widely investigated to treat ONFH, its therapeutic effects remain unsatisfactory. Therefore, further studies are required to determine op...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.20-0346
更新日期:2021-01-13 00:00:00
abstract::Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play key roles in the production of mature blood cells and in the biology and clinical outcomes of hematopoietic transplants. The numbers of these cells, however, are extremely low, particularly in umbilical cord blood (UCB); thus, ex vivo expan...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.5966/sctm.2013-0071
更新日期:2013-11-01 00:00:00
abstract::Functional hepatocytes, cardiomyocytes, neurons, and retinal pigment epithelial (RPE) cells derived from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) could provide a defined and renewable source of human cells relevant for cell replacement therapies, drug discovery, toxicology te...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2012-0047
更新日期:2013-02-01 00:00:00
abstract::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 m...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.17-0041
更新日期:2018-01-01 00:00:00
abstract:UNLABELLED:: Present therapies for stroke rest with tissue plasminogen activator (tPA), the sole licensed antithrombotic on the market; however, tPA's effectiveness is limited in that the drug not only must be administered less than 3-5 hours after stroke but often exacerbates blood-brain barrier (BBB) leakage and incr...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2014-0184
更新日期:2015-07-01 00:00:00