Cartilage repair using human embryonic stem cell-derived chondroprogenitors.

Abstract:

:In initial work, we developed a 14-day culture protocol under potential GMP, chemically defined conditions to generate chondroprogenitors from human embryonic stem cells (hESCs). The present study was undertaken to investigate the cartilage repair capacity of these cells. The chondrogenic protocol was optimized and validated with gene expression profiling. The protocol was also applied successfully to two lines of induced pluripotent stem cells (iPSCs). Chondrogenic cells derived from hESCs were encapsulated in fibrin gel and implanted in osteochondral defects in the patella groove of nude rats, and cartilage repair was evaluated by histomorphology and immunocytochemistry. Genes associated with chondrogenesis were upregulated during the protocol, and pluripotency-related genes were downregulated. Aggregation of chondrogenic cells was accompanied by high expression of SOX9 and strong staining with Safranin O. Culture with PluriSln1 was lethal for hESCs but was tolerated by hESC chondrogenic cells, and no OCT4-positive cells were detected in hESC chondrogenic cells. iPSCs were also shown to generate chondroprogenitors in this protocol. Repaired tissue in the defect area implanted with hESC-derived chondrogenic cells was stained for collagen II with little collagen I, but negligible collagen II was observed in the fibrin-only controls. Viable human cells were detected in the repair tissue at 12 weeks. The results show that chondrogenic cells derived from hESCs, using a chemically defined culture system, when implanted in focal defects were able to promote cartilage repair. This is a first step in evaluating these cells for clinical application for the treatment of cartilage lesions.

journal_name

Stem Cells Transl Med

authors

Cheng A,Kapacee Z,Peng J,Lu S,Lucas RJ,Hardingham TE,Kimber SJ

doi

10.5966/sctm.2014-0101

subject

Has Abstract

pub_date

2014-11-01 00:00:00

pages

1287-94

issue

11

eissn

2157-6564

issn

2157-6580

pii

sctm.2014-0101

journal_volume

3

pub_type

杂志文章
  • A Comparative Analysis of Attitudes on Communication Toward Stem Cell Research and Regenerative Medicine Between the Public and the Scientific Community.

    abstract::Owing to the rapid progress in stem cell research (SCR) and regenerative medicine (RM), society's expectation and interest in these fields are increasing. For effective communication on issues concerning SCR and RM, surveys for understanding the interests of stakeholders is essential. For this purpose, we conducted a ...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.17-0184

    authors: Shineha R,Inoue Y,Ikka T,Kishimoto A,Yashiro Y

    更新日期:2018-02-01 00:00:00

  • Concise review: pluripotent stem cell-based regenerative applications for failing β-cell function.

    abstract::Diabetes engenders the loss of pancreatic β-cell mass and/or function, resulting in insulin deficiency relative to the metabolic needs of the body. Diabetic care has traditionally relied on pharmacotherapy, exemplified by insulin replacement to target peripheral actions of the hormone. With growing understanding of th...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,评审

    doi:10.5966/sctm.2013-0184

    authors: Holditch SJ,Terzic A,Ikeda Y

    更新日期:2014-05-01 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

  • Concise Review: Translating Regenerative Biology into Clinically Relevant Therapies: Are We on the Right Path?

    abstract::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 of...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,评审

    doi:10.1002/sctm.17-0213

    authors: Simkin J,Seifert AW

    更新日期:2018-02-01 00:00:00

  • Proresolving Lipid Mediators and Receptors in Stem Cell Biology: Concise Review.

    abstract::Accumulating evidence indicates that stem cells (SCs) possess immunomodulatory, anti-inflammatory, and prohealing properties. The mechanisms underlying these functions are being investigated with the final goal to set a solid background for the clinical use of SCs and/or their derivatives. Specialized proresolving lip...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,评审

    doi:10.1002/sctm.19-0078

    authors: Romano M,Patruno S,Pomilio A,Recchiuti A

    更新日期:2019-10-01 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

  • Enhancing in vivo survival of adipose-derived stromal cells through Bcl-2 overexpression using a minicircle vector.

    abstract::Tissue regeneration using progenitor cell-based therapy has the potential to aid in the healing of a diverse range of pathologies, ranging from short-gut syndrome to spinal cord lesions. However, there are numerous hurdles to be overcome prior to the widespread application of these cells in the clinical setting. One o...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2013-0035

    authors: Hyun J,Grova M,Nejadnik H,Lo D,Morrison S,Montoro D,Chung M,Zimmermann A,Walmsley GG,Lee M,Daldrup-Link H,Wan DC,Longaker MT

    更新日期:2013-09-01 00:00:00

  • Epimuscular Fat in the Human Rotator Cuff Is a Novel Beige Depot.

    abstract:UNLABELLED:: Chronic rotator cuff (RC) tears are a common and debilitating injury, characterized by dramatic expansion of adipose tissue, muscle atrophy, and limited functional recovery. The role of adipose expansion in RC pathology is unknown; however, given the identified paracrine/endocrine regulation by other adipo...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2014-0287

    authors: Meyer GA,Gibbons MC,Sato E,Lane JG,Ward SR,Engler AJ

    更新日期:2015-07-01 00:00:00

  • Multipotent mesenchymal stromal cells synergize with costimulation blockade in the inhibition of immune responses and the induction of Foxp3+ regulatory T cells.

    abstract::Multipotent mesenchymal stromal cell (MSC) therapy and costimulation blockade are two immunomodulatory strategies being developed concomitantly for the treatment of immunological diseases. Both of these strategies have the capacity to inhibit immune responses and induce regulatory T cells; however, their ability to sy...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2014-0012

    authors: Takahashi T,Tibell A,Ljung K,Saito Y,Gronlund A,Osterholm C,Holgersson J,Lundgren T,Ericzon BG,Corbascio M,Kumagai-Braesch M

    更新日期:2014-12-01 00:00:00

  • Optimized serial expansion of human induced pluripotent stem cells using low-density inoculation to generate clinically relevant quantities in vertical-wheel bioreactors.

    abstract::Human induced pluripotent stem cells (hiPSCs) have generated a great deal of attention owing to their capacity for self-renewal and differentiation into the three germ layers of the body. Their discovery has facilitated a new era in biomedicine for understanding human development, drug screening, disease modeling, and...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.19-0406

    authors: Borys BS,So T,Colter J,Dang T,Roberts EL,Revay T,Larijani L,Krawetz R,Lewis I,Argiropoulos B,Rancourt DE,Jung S,Hashimura Y,Lee B,Kallos MS

    更新日期:2020-09-01 00:00:00

  • Concise Review: Is Cardiac Cell Therapy Dead? Embarrassing Trial Outcomes and New Directions for the Future.

    abstract::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 ce...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,评审

    doi:10.1002/sctm.17-0196

    authors: Tang JN,Cores J,Huang K,Cui XL,Luo L,Zhang JY,Li TS,Qian L,Cheng K

    更新日期:2018-04-01 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

  • 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

  • Impaired Angiogenic Potential of Human Placental Mesenchymal Stromal Cells in Intrauterine Growth Restriction.

    abstract:UNLABELLED:Human placental mesenchymal stromal cells (pMSCs) have never been investigated in intrauterine growth restriction (IUGR). We characterized cells isolated from placental membranes and the basal disc of six IUGR and five physiological placentas. Cell viability and proliferation were assessed every 7 days durin...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2015-0155

    authors: Mandò C,Razini P,Novielli C,Anelli GM,Belicchi M,Erratico S,Banfi S,Meregalli M,Tavelli A,Baccarin M,Rolfo A,Motta S,Torrente Y,Cetin I

    更新日期:2016-04-01 00:00:00

  • Cryopreserved Off-the-Shelf Allogeneic Adipose-Derived Stromal Cells for Therapy in Patients with Ischemic Heart Disease and Heart Failure-A Safety Study.

    abstract::The present first-in-human clinical trial evaluated the safety and feasibility of a newly developed and cryopreserved Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors for intramyocardial injection in ten patients with ischemic heart disease and ischemic heart failure (IHF...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.17-0040

    authors: Kastrup J,Haack-Sørensen M,Juhl M,Harary Søndergaard R,Follin B,Drozd Lund L,Mønsted Johansen E,Ali Qayyum A,Bruun Mathiasen A,Jørgensen E,Helqvist S,Jørgen Elberg J,Bruunsgaard H,Ekblond A

    更新日期:2017-11-01 00:00:00

  • Alteration of naïve and memory B-cell subset in chronic graft-versus-host disease patients after treatment with mesenchymal stromal cells.

    abstract::Although mesenchymal stromal cells (MSCs) possess immunomodulatory properties and exhibit promising efficacy against chronic graft-versus-host disease (cGVHD), little is known about the immune changes by which MSCs ameliorate cGVHD in vivo. Recent studies have suggested that B lymphocytes might play an important role ...

    journal_title:Stem cells translational medicine

    pub_type: 临床试验,杂志文章

    doi:10.5966/sctm.2014-0001

    authors: Peng Y,Chen X,Liu Q,Xu D,Zheng H,Liu L,Liu Q,Liu M,Fan Z,Sun J,Li X,Zou R,Xiang AP

    更新日期:2014-09-01 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

  • Adipose-derived mesenchymal stem cells reduce neuronal death after transient global cerebral ischemia through prevention of blood-brain barrier disruption and endothelial damage.

    abstract::Global cerebral ischemia (GCI) is the leading cause of a poor prognosis even after successful resuscitation from cardiac arrest. Therapeutic induction of hypothermia (TH) is the only proven therapy-and current standard care-for GCI after cardiac arrest; however, its application has been significantly limited owing to ...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2014-0103

    authors: Chung TN,Kim JH,Choi BY,Chung SP,Kwon SW,Suh SW

    更新日期:2015-02-01 00:00:00

  • Immature Midbrain Dopaminergic Neurons Derived from Floor-Plate Method Improve Cell Transplantation Therapy Efficacy for Parkinson's Disease.

    abstract::Recent reports have indicated human embryonic stem cells-derived midbrain dopamine (mDA) neurons as proper cell resources for use in Parkinson's disease (PD) therapy. Nevertheless, no detailed and systematic study has been conducted to identify which differentiation stages of mDA cells are most suitable for transplant...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.16-0470

    authors: Qiu L,Liao MC,Chen AK,Wei S,Xie S,Reuveny S,Zhou ZD,Hunziker W,Tan EK,Oh SKW,Zeng L

    更新日期:2017-09-01 00:00:00

  • 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...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.20-0269

    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

    更新日期:2020-11-23 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

  • Concise Review: Exploiting Unique Biological Features of Leukemia Stem Cells for Therapeutic Benefit.

    abstract::Cancer stem cells play a critical role in disease initiation and insensitivity to chemotherapy in numerous hematologic malignancies and some solid tumors, and these stem cells need to be eradicated to achieve a cure. Key to successful targeting of cancer stem cells is to identify and functionally test critical target ...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,评审

    doi:10.1002/sctm.18-0247

    authors: Zhang H,Li S

    更新日期:2019-08-01 00:00:00

  • Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial.

    abstract::Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with high mortality. Mesenchymal stem cells are known to exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in COVID-19 ARDS. The objective of this study was to determine safety and explore efficacy of umbilical c...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.20-0472

    authors: Lanzoni G,Linetsky E,Correa D,Messinger Cayetano S,Alvarez RA,Kouroupis D,Alvarez Gil A,Poggioli R,Ruiz P,Marttos AC,Hirani K,Bell CA,Kusack H,Rafkin L,Baidal D,Pastewski A,Gawri K,Leñero C,Mantero AMA,Metalonis SW

    更新日期:2021-01-05 00:00:00

  • Rescue of an in vitro neuron phenotype identified in Niemann-Pick disease, type C1 induced pluripotent stem cell-derived neurons by modulating the WNT pathway and calcium signaling.

    abstract::Niemann-Pick disease, type C1 (NPC1) is a familial disorder that has devastating consequences on postnatal development with multisystem effects, including neurodegeneration. There is no Food and Drug Administration-approved treatment option for NPC1; however, several potentially therapeutic compounds have been identif...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2014-0127

    authors: Efthymiou AG,Steiner J,Pavan WJ,Wincovitch S,Larson DM,Porter FD,Rao MS,Malik N

    更新日期:2015-03-01 00:00:00

  • Synthetic mRNA-based differentiation method enables early detection of Parkinson's phenotypes in neurons derived from Gaucher disease-induced pluripotent stem cells.

    abstract::Gaucher disease, the most prevalent metabolic storage disorder, is caused by mutations in the glucocerebrosidase gene GBA1, which lead to the accumulation of glucosylceramide (GlcCer) in affected cells. Gaucher disease type 1 (GD1), although defined as nonneuronopathic subtype, is accompanied by an increased risk of P...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.20-0302

    authors: Akiyama T,Sato S,Ko SBH,Sano O,Sato S,Saito M,Nagai H,Ko MSH,Iwata H

    更新日期:2020-12-20 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

  • Efficient lentiviral transduction of human mesenchymal stem cells that preserves proliferation and differentiation capabilities.

    abstract::Long-term lentiviral transduction of human mesenchymal stem cells (hMSCs) greatly enhances the usefulness of these cells. However, such transduction currently requires the use of polybrene, which severely inhibits hMSC proliferation. In contrast, protamine sulfate at 100 μg/ml doubled transduction efficiencies without...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2012-0086

    authors: Lin P,Lin Y,Lennon DP,Correa D,Schluchter M,Caplan AI

    更新日期:2012-12-01 00:00:00

  • Cell Therapy for Chronic Limb-Threatening Ischemia: Current Evidence and Future Directions.

    abstract::Cell-based therapies have gained interest as a potential treatment method in cardiovascular disease in the past two decades, peripheral artery disease amongst others. Initial pre-clinical and small pilot clinical studies showed promising effects of cell therapy in peripheral artery disease and chronic limb-threatening...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.18-0025

    authors: Teraa M,Gremmels H,Wijnand JGJ,Verhaar MC

    更新日期:2018-12-01 00:00:00

  • Concise review: mesenchymal stem cells and translational medicine: emerging issues.

    abstract::Mesenchymal stem cells (MSCs) are emerging as a promising therapeutic approach of cell-based therapy for a wide range of autoimmune disorders and degenerative diseases. In preclinical and clinical studies, MSCs have been shown to be highly efficient in treating graft-versus-host disease, systemic lupus erythematosus, ...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,评审

    doi:10.5966/sctm.2011-0019

    authors: Ren G,Chen X,Dong F,Li W,Ren X,Zhang Y,Shi Y

    更新日期:2012-01-01 00:00:00

  • Human Lung Spheroids as In Vitro Niches of Lung Progenitor Cells with Distinctive Paracrine and Plasticity Properties.

    abstract::Basic and translational research on lung biology has discovered multiple progenitor cell types, specialized or facultative, responsible for turnover, renewal, and repair. Isolation of populations of resident lung progenitor cells (LPCs) has been described by multiple protocols, and some have been successfully applied ...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2015-0374

    authors: Chimenti I,Pagano F,Angelini F,Siciliano C,Mangino G,Picchio V,De Falco E,Peruzzi M,Carnevale R,Ibrahim M,Biondi-Zoccai G,Messina E,Frati G

    更新日期:2017-03-01 00:00:00