A robust culture system to generate neural progenitors with gliogenic competence from clinically relevant induced pluripotent stem cells for treatment of spinal cord injury.

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 Med

authors

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 J

doi

10.1002/sctm.20-0269

subject

Has Abstract

pub_date

2020-11-23 00:00:00

eissn

2157-6564

issn

2157-6580

pub_type

杂志文章
  • Brachyury engineers cardiac repair competent stem cells.

    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

    authors: Li M,Yamada S,Shi A,Singh RD,Rolland TJ,Jeon R,Lopez N,Shelerud L,Terzic A,Behfar A

    更新日期:2020-10-24 00:00:00

  • Lung Injury Repair by Transplantation of Adult Lung Cells Following Preconditioning of Recipient Mice.

    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

    authors: Milman Krentsis I,Rosen C,Shezen E,Aronovich A,Nathanson B,Bachar-Lustig E,Berkman N,Assayag M,Shakhar G,Feferman T,Orgad R,Reisner Y

    更新日期:2018-01-01 00:00:00

  • Hierarchy of breast cancer cells: key to reverse dormancy for therapeutic intervention.

    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

    authors: Bliss SA,Greco SJ,Rameshwar P

    更新日期:2014-07-01 00:00:00

  • Dynamic Changes in Brain Mesenchymal Perivascular Cells Associate with Multiple Sclerosis Disease Duration, Active Inflammation, and Demyelination.

    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

    authors: Iacobaeus E,Sugars RV,Törnqvist Andrén A,Alm JJ,Qian H,Frantzen J,Newcombe J,Alkass K,Druid H,Bottai M,Röyttä M,Le Blanc K

    更新日期:2017-10-01 00:00:00

  • Sustained knockdown of a disease-causing gene in patient-specific induced pluripotent stem cells using lentiviral vector-based gene therapy.

    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

    authors: Eggenschwiler R,Loya K,Wu G,Sharma AD,Sgodda M,Zychlinski D,Herr C,Steinemann D,Teckman J,Bals R,Ott M,Schambach A,Schöler HR,Cantz T

    更新日期:2013-09-01 00:00:00

  • Directing Differentiation of Pluripotent Stem Cells Toward Retinal Pigment Epithelium Lineage.

    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

    authors: Choudhary P,Booth H,Gutteridge A,Surmacz B,Louca I,Steer J,Kerby J,Whiting PJ

    更新日期:2017-02-01 00:00:00

  • Distinct mobilization of circulating CD271+ mesenchymal progenitors from hematopoietic progenitors during aging and after myocardial infarction.

    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

    authors: Iso Y,Yamaya S,Sato T,Poole CN,Isoyama K,Mimura M,Koba S,Kobayashi Y,Takeyama Y,Spees JL,Suzuki H

    更新日期:2012-06-01 00:00:00

  • PTEN Promotes Dopaminergic Neuronal Differentiation Through Regulation of ERK-Dependent Inhibition of S6K Signaling in Human Neural Stem Cells.

    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

    authors: Lee JE,Lim MS,Park JH,Park CH,Koh HC

    更新日期:2016-10-01 00:00:00

  • Functional and Transcriptional Characterization of Histone Deacetylase Inhibitor-Mediated Cardiac Adverse Effects in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

    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

    authors: Kopljar I,Gallacher DJ,De Bondt A,Cougnaud L,Vlaminckx E,Van den Wyngaert I,Lu HR

    更新日期:2016-05-01 00:00:00

  • Osteogenic Stimulation of Human Adipose-Derived Mesenchymal Stem Cells Using a Fungal Metabolite That Suppresses the Polycomb Group Protein EZH2.

    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

    authors: Samsonraj RM,Dudakovic A,Manzar B,Sen B,Dietz AB,Cool SM,Rubin J,van Wijnen AJ

    更新日期:2018-02-01 00:00:00

  • Identification and isolation of small CD44-negative mesenchymal stem/progenitor cells from human bone marrow using elutriation and polychromatic flow cytometry.

    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

    authors: Hall SR,Jiang Y,Leary E,Yavanian G,Eminli S,O'Neill DW,Marasco WA

    更新日期:2013-08-01 00:00:00

  • Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Expanded In Vitro for Treatment of Aplastic Anemia: A Multicenter Phase II Trial.

    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

    authors: Pang Y,Xiao HW,Zhang H,Liu ZH,Li L,Gao Y,Li HB,Jiang ZJ,Tan H,Lin JR,Du X,Weng JY,Nie DN,Lin DJ,Zhang XZ,Liu QF,Xu DR,Chen HJ,Ge XH,Wang XY,Xiao Y

    更新日期:2017-07-01 00:00:00

  • Cross talk between mesenchymal and glioblastoma stem cells: Communication beyond controversies.

    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

    authors: Bajetto A,Thellung S,Dellacasagrande I,Pagano A,Barbieri F,Florio T

    更新日期:2020-11-01 00:00:00

  • The emerging antioxidant paradigm of mesenchymal stem cell therapy.

    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

    authors: Stavely R,Nurgali K

    更新日期:2020-09-01 00:00:00

  • Regeneration of Full-Thickness Rotator Cuff Tendon Tear After Ultrasound-Guided Injection With Umbilical Cord Blood-Derived Mesenchymal Stem Cells in a Rabbit Model.

    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

    authors: Park GY,Kwon DR,Lee SC

    更新日期:2015-11-01 00:00:00

  • Bone marrow mesenchymal stem cell transplantation retards the natural senescence of rat hearts.

    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

    authors: Zhang M,Liu D,Li S,Chang L,Zhang Y,Liu R,Sun F,Duan W,Du W,Wu Y,Zhao T,Xu C,Lu Y

    更新日期:2015-05-01 00:00:00

  • Humanized culture of periosteal progenitors in allogeneic serum enhances osteogenic differentiation and in vivo bone formation.

    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

    authors: Roberts SJ,Owen HC,Tam WL,Solie L,Van Cromphaut SJ,Van den Berghe G,Luyten FP

    更新日期:2014-02-01 00:00:00

  • Viral pandemic preparedness: A pluripotent stem cell-based machine-learning platform for simulating SARS-CoV-2 infection to enable drug discovery and repurposing.

    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

    authors: Esmail S,Danter W

    更新日期:2021-02-01 00:00:00

  • Therapeutic Prospective of Infused Allogenic Cultured Mesenchymal Stem Cells in Traumatic Brain Injury Mice: A Longitudinal Proton Magnetic Resonance Spectroscopy Assessment.

    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

    authors: Mishra SK,Rana P,Khushu S,Gangenahalli G

    更新日期:2017-01-01 00:00:00

  • Reliable generation of induced pluripotent stem cells from human lymphoblastoid cell lines.

    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

    authors: Barrett R,Ornelas L,Yeager N,Mandefro B,Sahabian A,Lenaeus L,Targan SR,Svendsen CN,Sareen D

    更新日期:2014-12-01 00:00:00

  • Oral Mucosal Lamina Propria-Progenitor Cells Exert Antibacterial Properties via the Secretion of Osteoprotegerin and Haptoglobin.

    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

    authors: Board-Davies E,Moses R,Sloan A,Stephens P,Davies LC

    更新日期:2015-11-01 00:00:00

  • Comparison of Different Cytokine Conditions Reveals Resveratrol as a New Molecule for Ex Vivo Cultivation of Cord Blood-Derived Hematopoietic Stem Cells.

    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

    authors: Heinz N,Ehrnström B,Schambach A,Schwarzer A,Modlich U,Schiedlmeier B

    更新日期:2015-09-01 00:00:00

  • Antifibrotic Activity of Human Placental Amnion Membrane-Derived CD34+ Mesenchymal Stem/Progenitor Cell Transplantation in Mice With Thioacetamide-Induced Liver Injury.

    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

    authors: Lee PH,Tu CT,Hsiao CC,Tsai MS,Ho CM,Cheng NC,Hung TM,Shih DT

    更新日期:2016-11-01 00:00:00

  • Anti-inflammatory mesenchymal stem cells (MSC2) attenuate symptoms of painful diabetic peripheral neuropathy.

    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

    authors: Waterman RS,Morgenweck J,Nossaman BD,Scandurro AE,Scandurro SA,Betancourt AM

    更新日期:2012-07-01 00:00:00

  • Enhanced Immunosuppression of T Cells by Sustained Presentation of Bioactive Interferon-γ Within Three-Dimensional Mesenchymal Stem Cell Constructs.

    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

    authors: Zimmermann JA,Hettiaratchi MH,McDevitt TC

    更新日期:2017-01-01 00:00:00

  • Cotransplantation of mesenchymal stem cells and endothelial progenitor cells for treating steroid-induced osteonecrosis of the femoral head.

    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

    authors: Xu H,Wang C,Liu C,Peng Z,Li J,Jin Y,Wang Y,Guo J,Zhu L

    更新日期:2021-01-13 00:00:00

  • Concise review: ex vivo expansion of cord blood-derived hematopoietic stem and progenitor cells: basic principles, experimental approaches, and impact in regenerative medicine.

    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

    authors: Flores-Guzmán P,Fernández-Sánchez V,Mayani H

    更新日期:2013-11-01 00:00:00

  • Comparative analysis of targeted differentiation of human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells reveals variability associated with incomplete transgene silencing in retrovirally derived hiPSC lines.

    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

    authors: Toivonen S,Ojala M,Hyysalo A,Ilmarinen T,Rajala K,Pekkanen-Mattila M,Äänismaa R,Lundin K,Palgi J,Weltner J,Trokovic R,Silvennoinen O,Skottman H,Narkilahti S,Aalto-Setälä K,Otonkoski T

    更新日期:2013-02-01 00:00:00

  • Multiple Autologous Bone Marrow-Derived CD271+ Mesenchymal Stem Cell Transplantation Overcomes Drug-Resistant Epilepsy in Children.

    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

    authors: Milczarek O,Jarocha D,Starowicz-Filip A,Kwiatkowski S,Badyra B,Majka M

    更新日期:2018-01-01 00:00:00

  • Bystander Effect Fuels Human Induced Pluripotent Stem Cell-Derived Neural Stem Cells to Quickly Attenuate Early Stage Neurological Deficits After Stroke.

    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

    authors: Eckert A,Huang L,Gonzalez R,Kim HS,Hamblin MH,Lee JP

    更新日期:2015-07-01 00:00:00