Abstract:
:Standardization guidelines for human pluripotent stem cells are still very broadly defined, despite ongoing clinical trials in the U.S., U.K., and Japan. The requirements for validation of human embryonic (hESCs) and induced pluripotent stem cells (iPSCs) in general follow the regulations for other clinically compliant biologics already in place but without addressing key differences between cell types or final products. In order to realize the full potential of stem cell therapy, validation criteria, methodology, and, most importantly, strategy, should address the shortfalls and efficiency of current approaches; without this, hESC- and, especially, iPSC-based therapy will not be able to compete with other technologies in a cost-efficient way. We addressed the protocols for testing cell lines for human viral pathogens and propose a novel strategy that would significantly reduce costs. It is highly unlikely that the multiple cell lines derived in parallel from a tissue sample taken from one donor would have different profiles of endogenous viral pathogens; we therefore argue that samples from the Master Cell Banks of sibling lines could be safely pooled for validation. We illustrate this approach with tiered validation of two sibling clinical-grade hESC lines, KCL033 and KCL034 (stage 1, sterility; stage 2, specific human pathogens; and stage 3, nonspecific human pathogens). The results of all tests were negative. This cost-effective strategy could also be applied for validation of Master Cell Banks of multiple clinical-grade iPSC lines derived from a single donor.
journal_name
Stem Cells Transl Medjournal_title
Stem cells translational medicineauthors
Devito L,Petrova A,Miere C,Codognotto S,Blakely N,Lovatt A,Ogilvie C,Khalaf Y,Ilic Ddoi
10.5966/sctm.2014-0015subject
Has Abstractpub_date
2014-10-01 00:00:00pages
1116-24issue
10eissn
2157-6564issn
2157-6580pii
sctm.2014-0015journal_volume
3pub_type
杂志文章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
更新日期:2014-12-01 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::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::Adipose-derived stem cells (ASCs) are being tested in clinical trials related to cell-based regenerative therapies. Although most of the current expansion protocols for ASCs use fetal calf serum (FCS), xenogeneic-free medium supplements are greatly desired. This study aims to compare the effect of FCS, human platelet ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0148
更新日期:2016-03-01 00:00:00
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
更新日期:2012-12-01 00:00:00
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
更新日期:2018-04-01 00:00:00
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
更新日期:2014-09-01 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:UNLABELLED:: Induced pluripotent stem cells (iPSCs) are new diagnostic and potentially therapeutic tools to model disease and assess the toxicity of pharmaceutical medications. A common limitation of cell lineages derived from iPSCs is a blunted phenotype compared with fully developed, endogenous cells. We examined the...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0235
更新日期:2016-09-01 00:00:00
abstract::Cardiovascular disease is a major cause of morbidity and mortality, especially in developed countries. Various therapies for cardiovascular disease are investigated actively and are performed clinically. Recently, cell-based regenerative medicine using several cell sources has appeared as an alternative therapy for cu...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.5966/sctm.2012-0030
更新日期:2012-02-01 00:00:00
abstract::Device-encapsulated human stem cell-derived pancreatic endoderm (PE) can generate functional β-cell implants in the subcutis of mice, which has led to the start of clinical studies in type 1 diabetes. Assessment of the formed functional β-cell mass (FBM) and its correlation with in vivo metabolic markers can guide cli...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.19-0043
更新日期:2019-12-01 00:00:00
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
更新日期:2017-11-01 00:00:00
abstract:UNLABELLED:: Recapitulation of endochondral ossification (ECO) (i.e., generation of marrow-containing ossicles through a cartilage intermediate) has relevance to develop human organotypic models for bone or hematopoietic cells and to engineer grafts for bone regeneration. Unlike bone marrow-derived stromal cells (also ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0256
更新日期:2016-08-01 00:00:00
abstract::Muscle-derived stem cells (MDSCs) isolated from mouse skeletal muscle by a modified preplate technique exhibit long-term proliferation, high self-renewal, and multipotent differentiation capabilities in vitro. MDSCs retrovirally transduced to express bone morphogenetic proteins (BMPs) can differentiate into osteocytes...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2013-0027
更新日期:2013-09-01 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: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::Knee osteoarthritis (OA) is a leading cause of pain and disability. Although conventional treatments show modest benefits, pilot and phase I/II trials with bone marrow (BM) and adipose-derived (AD) mesenchymal stromal cells (MSCs) point to the feasibility, safety, and occurrence of clinical and structural improvement ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,随机对照试验
doi:10.1002/sctm.18-0053
更新日期:2019-03-01 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
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::There has been considerable progress in obtaining engraftable embryonic stem (ES) cell-derived midbrain dopamine neurons for cell replacement therapy in models of Parkinson's disease; however, limited integration and striatal reinnervation of ES-derived grafts remain a major challenge for future clinical translation. ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2013-0084
更新日期:2014-01-01 00:00:00
abstract::Biomimetic scaffolds are extremely versatile in terms of chemical composition and physical properties, which can be defined to accomplish specific applications. One property that can be added is the production/release of bioactive soluble factors, either directly from the biomaterial, or from cells embedded within the...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.18-0085
更新日期:2019-01-01 00:00:00
abstract::Adult hemoglobin composed of α- and β-globin reflects a change from expression of embryonic ε- and fetal γ-globin to adult β-globin in human erythroid cells, so-called globin switching. Human pluripotent stem cells (hPSCs) are a potential source for in vitro erythrocyte production, but they show prominent expression o...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2013-0216
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::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 ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.18-0230
更新日期:2019-05-01 00:00:00
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
更新日期:2020-11-23 00:00:00
abstract::Perivascular stem cells (PSCs) are the natural ancestors of mesenchymal stem cells (MSCs) and are the stem cells responsible for homeostasis and repair in vivo. Prospectively identified and isolated PSCs have demonstrated increased plasticity and osteogenic potential. Cells from the infrapatellar fat pad (IFP) have de...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2016-0040
更新日期:2017-01-01 00:00:00
abstract::High-dose chemotherapy is accompanied by an obligate period of neutropenia. Resulting bacterial and fungal infections are the leading cause of morbidity and mortality in neutropenic patients despite prophylactic antimicrobials and hematopoietic growth factor supplements. Replacing neutrophils in the patient through tr...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.5966/sctm.2013-0145
更新日期:2014-04-01 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::Induced pluripotent stem cells (iPSCs) have elicited excitement in both the scientific and ethics communities for their potential to advance basic and translational research. They have been hailed as an alternative to derivation from embryos that provides a virtually unlimited source of pluripotent stem cells for rese...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2012-0029
更新日期:2012-05-01 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