Abstract:
:Cell therapy has attracted considerable interest as a promising therapeutic alternative for patients with Parkinson's disease (PD). Clinical studies have shown that grafted fetal neural tissue can achieve considerable biochemical and clinical improvements in PD. However, the source of fetal tissue grafts is limited and ethically controversial. Human parthenogenetic stem cells offer a good alternative because they are derived from unfertilized oocytes without destroying potentially viable human embryos and can be used to generate an unlimited supply of neural cells for transplantation. We have previously reported that human parthenogenetic stem cell-derived neural stem cells (hpNSCs) successfully engraft, survive long term, and increase brain dopamine (DA) levels in rodent and nonhuman primate models of PD. Here we report the results of a 12-month transplantation study of hpNSCs in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned African green monkeys with moderate to severe clinical parkinsonian symptoms. The hpNSCs manufactured under current good manufacturing practice (cGMP) conditions were injected bilaterally into the striatum and substantia nigra of immunosuppressed monkeys. Transplantation of hpNSCs was safe and well tolerated by the animals with no dyskinesia, tumors, ectopic tissue formation, or other test article-related serious adverse events. We observed that hpNSCs promoted behavioral recovery; increased striatal DA concentration, fiber innervation, and number of dopaminergic neurons; and induced the expression of genes and pathways downregulated in PD compared to vehicle control animals. These results provide further evidence for the clinical translation of hpNSCs and support the approval of the world's first pluripotent stem cell-based phase I/IIa study for the treatment of PD (Clinical Trial Identifier NCT02452723).
journal_name
Cell Transplantjournal_title
Cell transplantationauthors
Gonzalez R,Garitaonandia I,Poustovoitov M,Abramihina T,McEntire C,Culp B,Attwood J,Noskov A,Christiansen-Weber T,Khater M,Mora-Castilla S,To C,Crain A,Sherman G,Semechkin A,Laurent LC,Elsworth JD,Sladek J,Snyder EY,doi
10.3727/096368916X691682subject
Has Abstractpub_date
2016-11-01 00:00:00pages
1945-1966issue
11eissn
0963-6897issn
1555-3892pii
content-CT-1518_Gonzalez_et_aljournal_volume
25pub_type
杂志文章abstract::An important challenge in pancreatic islet transplantation in association with type 1 diabetes is to define automatic high-throughput assays for evaluation of human islet function. The physiological techniques presently used are amenable to small-scale experimental samples and produce descriptive results. The postgeno...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:
更新日期:2008-01-01 00:00:00
abstract::At present, there are still significant barriers that impede the clinical use of hESCs and iPS cells, including ethics, immunorejection, tumorigenesis from hESCs, and teratoma formation from iPS cells. It is therefore necessary to search for alternative sources of stem cells. WJ-MSCs originate from embryonic epiblasts...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368912X662444
更新日期:2013-01-01 00:00:00
abstract::The human neuronal cell-1 (HCN-1) line has recently been established. Under favorable conditions, these cells differentiate into mature neuronal phenotypes. Here we report on further characterization of these cells. Cultured HCN-1 cells express fibronectin immunoreactivity and grow well on fibronectin substrate but do...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/096368979200100104
更新日期:1992-01-01 00:00:00
abstract::Current good manufacturing practice (cGMP) islet processing facilities provide an ultraclean environment for the safe production of clinical grade islets for transplantation into immunosuppressed diabetic recipients. The objective of this study was to monitor the rate of microbial contamination in islet products after...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract::Stem cell-based therapy shows great potential in stroke patients. Intra-artery infusion exhibits greater biological distribution compared to intravenous delivery. In addition, umbilical cord mesenchymal stem cells (UCMSCs) have several advantages compared with other types of stem cells. The aim of this study was to ev...
journal_title:Cell transplantation
pub_type: 临床试验,杂志文章
doi:10.3727/096368912X658818
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Extracellular vesicles (EVs) released from mesenchymal stem/stromal cells (MSCs) mediate their paracrine effect, but their efficacy to protect the microcirculation of the kidney is unknown. Using a novel swine model of unilateral renovascular disease (RVD) complicated by metabolic syndrome (MetS), we tested ...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/0963689718780942
更新日期:2018-07-01 00:00:00
abstract::Islet isolation involves enzymatic digestion of the interstitial matrix and mechanical disruption of the tissue. It is possible that a fundamental change of islet biology resulting from the loss of critical factors required for islet function or survival will occur. Extracellular matrix (ECM) is one of the most import...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract::Successful transplantation of cadaver embryonic neural tissue is highly dependent on the method used to obtain the tissue. It is important that the tissue not be contaminated bacteriologically by vaginal flora during the procedure, and that it not be disrupted mechanically. A low-pressure aspiration abortion technique...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/096368979400300202
更新日期:1994-03-01 00:00:00
abstract::Hepatocyte transplantation is dependent on the availability of good quality human hepatocytes isolated from donor liver tissue. Hepatocytes obtained from livers rejected for transplantation on the grounds of steatosis are often of low viability and not suitable for clinical use. The aim of this study was to evaluate t...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368910X514620
更新日期:2010-01-01 00:00:00
abstract::Recent advances in islet transplantation using highly purified islets and effective immunosuppression strategies have resulted in substantial improvement in achieving insulin independence in type 1 diabetes patients. However, there are side effects from long-term immunosuppression, and transplant rejection and/or the ...
journal_title:Cell transplantation
pub_type: 杂志文章,评审
doi:10.3727/000000008783907107
更新日期:2008-01-01 00:00:00
abstract::Embryonic stem (ES) cells have the ability to generate teratomas when transplanted into immunodeficient mice, but conditions affecting the generation remain to be elucidated. Nonhuman primate cynomolgus ES cells were transplanted into immunodeficient mice under different conditions; the number of transplanted cells, p...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368908786991560
更新日期:2008-09-01 00:00:00
abstract::To learn more about nonimmune-mediated islet graft failure, we transplanted different preparations (preps) of isolated human islets under the kidney capsule of streptozotocin (STZ)-diabetic nude mice. One month after the implantation of 1,000 or 2,000 islets, grafts were harvested for morphological, immunohistochemica...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368908787648137
更新日期:2008-01-01 00:00:00
abstract::The hypogonadal (HPG) mouse is a mutant that lacks a functional gonadotropin-releasing hormone (GnRH) gene. In this study, female HPG mice received bilateral intrahypothalamic implants of an immortalized GnRH-secreting cell line (GT1-7). Nine mice were tested 42- 65 days after implantation to determine whether these c...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/096368979300200309
更新日期:1993-05-01 00:00:00
abstract::Adipose tissue contains a mesenchymal stem cell (MSC) population known as adipose-derived stem cells (ASCs) capable of differentiating into different cell types. Our aim was to induce hepatic transdifferentiation of ASCs by sequential exposure to several combinations of cytokines, growth factors, and hormones. The mos...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368909X12483162197321
更新日期:2009-01-01 00:00:00
abstract::Major skin burns are difficult to treat. Patients often require special care and long-term hospitalization. Besides specific complications associated with the wounds themselves, there may be impairment of the immune system and of other organs. Mesenchymal stromal cells (MSCs) are a recent therapeutic alternative to tr...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368915X688128
更新日期:2016-01-01 00:00:00
abstract::In our previous study, intracerebral implantation of peripheral blood stem cells (PBSCs) improved functional outcome in rats with chronic cerebral infarction. Based on this finding, a randomized, single blind controlled study was conducted in 30 patients [PBSC group (n = 15) and control group (n = 15)] with middle cer...
journal_title:Cell transplantation
pub_type: 杂志文章,随机对照试验
doi:10.3727/096368914X678562
更新日期:2014-01-01 00:00:00
abstract::This study was designed to investigate functional recovery after the transplantation of mesenchymal stem cells (MSCs) or neurally differentiated MSCs (NMSCs) derived from bone marrow in a rat model of spinal cord injury (SCI). Sprague-Dawley rats were subjected to incomplete SCI using an NYU impactor to create a free ...
journal_title:Cell transplantation
pub_type: 杂志文章,已发布勘误
doi:10.3727/096368916X692078
更新日期:2016-07-01 00:00:00
abstract::Nerve growth factor (NGF) exerts both trophic (cell survival) and tropic (axonal growth-promoting) effects on several neuronal populations. In particular, its robust ability to prevent lesion-induced and spontaneous age-related basal forebrain cholinergic neuronal degeneration, and to promote mnemonic recovery, has su...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/096368970000900508
更新日期:2000-09-01 00:00:00
abstract::The major limitation of nonhuman primate (NHP) embryonic stem (ES) cell research is inefficient genetic modification and limited knowledge of differentiation mechanisms. A genetically modified NHP-ES cell with biomarkers, such as green fluorescent protein (GFP), that allow noninvasive monitoring of transgenic cells, i...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/000000002783985350
更新日期:2002-01-01 00:00:00
abstract::Multilineage-differentiating stress-enduring (Muse) cells are endogenous pluripotent stem cells that can be isolated based on stage-specific embryonic antigen-3 (SSEA-3), a pluripotent stem cell-surface marker. However, their capacities for survival, neurotrophic factor secretion, and neuronal and glial differentiatio...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/0963689719863809
更新日期:2019-09-01 00:00:00
abstract::Procurement of multipotential neuroglial stem cells is possible with the addition of epidermal growth factor (EGF). Stem cells will differentiate into neurons and glia upon the removal of EGF from the culture medium. We have previously characterized the neuronal differentiation of stem cells derived from long-term cul...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1016/0963-6897(95)02043-8
更新日期:1996-03-01 00:00:00
abstract::Mononuclear stem cells have been studied for their potential in myocardial ischemia. In our previous published article, ReACT(®) phase I/II clinical trial, our results suggest that a certain cell population, promonocytes, directly correlated with the perceived angiogenesis in refractory angina patients. This study is ...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368914X681595
更新日期:2015-01-01 00:00:00
abstract::Hepatocyte transplantation has been proposed as a technique for bridging patients to whole-organ transplantation, for providing metabolic support during liver failure, and for replacing whole-organ transplantation in certain metabolic liver diseases. Assessment of hepatocyte engraftment has been difficult to measure, ...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/000000004783983945
更新日期:2004-01-01 00:00:00
abstract::Pancreatic islet transplantation is limited by shortage of donor organs. Although beta-cell lines could be used, their secretion of insulin is characteristically glucose independent and immunoisolation is required. Here we show that intrasplenic transplantation of encapsulated glucose-responsive mouse insulinoma cells...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/000000005783982990
更新日期:2005-01-01 00:00:00
abstract::Cell and tissue culture techniques have improved considerably since the first attempts to maintain explants of animal tissue in vitro. The two major developments that have allowed these improvements are the ability to produce continuous cell lines, thus allowing reproducible results to be obtained, and the definition ...
journal_title:Cell transplantation
pub_type: 杂志文章,评审
doi:10.1016/0963-6897(95)02005-5
更新日期:1996-01-01 00:00:00
abstract::Human amniotic membrane (hAM) is the innermost layer of fetal membranes, which surrounds the developing fetus and forms the amniotic cavity. hAM and hAM-derived cells possess many properties that make them suitable for use in regenerative medicine, such as low immunogenicity, promotion of epithelization, anti-inflamma...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/0963689717725528
更新日期:2018-01-01 00:00:00
abstract::Regenerative medicine is a new field primarily based on the concept of transplanting exogenous or stimulating endogenous stem cells to generate biological substitutes and improve tissue functions. Recently, amnion-derived cells have been reported to have multipotent differentiation ability, and these cells have attrac...
journal_title:Cell transplantation
pub_type: 杂志文章,评审
doi:10.3727/096368909788341243
更新日期:2009-01-01 00:00:00
abstract::Hypoxia is an adverse condition that can jeopardize the function of a bioartificial pancreatic construct. In this study we have investigated the effects of short-term hypoxic exposure (up to 24 h) on the bioenergetic status, metabolism, and insulin secretion of perfused pancreatic constructs composed of alginate/poly-...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/096368970000900312
更新日期:2000-05-01 00:00:00
abstract::We here present an immunologic head-to-head comparison between human umbilical cord lining mesenchymal stem cells (clMSCs) and adult bone marrow MSCs (bmMSCs) from patients >65 years of age. clMSCs had significantly lower HLA class I expression, higher production of tolerogenic TGF-β and IL-10, and showed significantl...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368910X536473
更新日期:2011-01-01 00:00:00
abstract::The nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D) was discovered by coincidence in the 1980s and has since been widely used in the investigation of T1D and diabetic complications. The current in vivo study was originally designed to prospectively assess whether hyperglycemia onset is associated with phy...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/0963689720939127
更新日期:2020-01-01 00:00:00