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 homing of systemically infused allogeneic MSCs preprostatectomy was conducted. The primary objective was to assess safety and feasibility and to determine if MSCs accumulate within primary PC tissue. MSCs were quantified using beads, emulsion, amplification, magnetics digital polymerase chain reaction (limit of detection: ≥0.01% MSCs) to measure allogeneic MSC DNA relative to recipient DNA. MSCs were harvested from healthy donors and expanded ex vivo using standard protocols by the Johns Hopkins Cell Therapy Laboratory. PC patients planning to undergo prostatectomy were eligible for MSC infusion. Enrolled subjects received a single intravenous infusion 4-6 days prior to prostatectomy. The first three subjects received 1 x 106 cells per kilogram (maximum 1 x 108 cells), and subsequent four patients received 2 x 106 cells per kilogram (maximum 2 x 108 cells). No dose-limiting toxicities were observed and all patients underwent prostatectomy without delay. Pathologic assessment of prostate cores revealed ≥70% tumor involvement in cores from four subjects, with benign tissue in the others. MSCs were undetectable in all subjects, and the study was stopped early for futility. MSC infusions appear safe in PC patients. Although intended for eventual use in metastatic PC patients, in this study, MSCs did not home primary tumors in sufficient levels to warrant further development as a cell-based therapeutic delivery strategy using standard ex vivo expansion protocols. Stem Cells Translational Medicine 2019;8:441-449.
journal_name
Stem Cells Transl Medjournal_title
Stem cells translational medicineauthors
Schweizer MT,Wang H,Bivalacqua TJ,Partin AW,Lim SJ,Chapman C,Abdallah R,Levy O,Bhowmick NA,Karp JM,De Marzo A,Isaacs JT,Brennen WN,Denmeade SRdoi
10.1002/sctm.18-0230subject
Has Abstractpub_date
2019-05-01 00:00:00pages
441-449issue
5eissn
2157-6564issn
2157-6580journal_volume
8pub_type
杂志文章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::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::Breast cancer-related lymphedema (BCRL) is a debilitating late complication with a lack of treatment opportunities. Recent studies have suggested that mesenchymal stromal cells can alleviate lymphedema. Herein, we report the results from the first human pilot study with freshly isolated adipose-derived regenerative ce...
journal_title:Stem cells translational medicine
pub_type: 临床试验,杂志文章
doi:10.1002/sctm.17-0037
更新日期:2017-08-01 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::: Fast remyelination by endogenous oligodendrocyte precursor cells (OPCs) is essential to prevent axonal and subsequent retrograde neuronal degeneration in demyelinating lesions in multiple sclerosis (MS). In chronic lesions, however, the remyelination capacity of OPCs becomes insufficient. Cell therapy with exogenous...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2016-0024
更新日期:2016-11-01 00:00:00
abstract::Gaucher disease (GD) is the most common lysosomal storage disease resulting from mutations in the lysosomal enzyme glucocerebrosidase (GCase). The hematopoietic abnormalities in GD include the presence of characteristic Gaucher macrophages that infiltrate patient tissues and cytopenias. At present, it is not clear whe...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2014-0213
更新日期:2015-08-01 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:UNLABELLED:We evaluated the association of diabetes and insulin resistance with the response to cell therapy in patients with nonischemic dilated cardiomyopathy (DCM). A total of 45 outpatients with DCM received granulocyte colony-stimulating factor for 5 days. CD34(+) cells were then collected by apheresis and injecte...
journal_title:Stem cells translational medicine
pub_type: 临床试验,杂志文章
doi:10.5966/sctm.2015-0172
更新日期:2016-05-01 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::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
更新日期:2020-09-01 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::Cellular therapy is enabling new approaches to tackle significant unmet needs in areas such as regenerative medicine and immunotherapy. The pharmacology of cell therapeutics becomes of critical importance to assure that these new drugs work reproducibly and effectively. Cell pharmacology can benefit from adapting prin...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.19-0019
更新日期:2019-09-01 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::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::Diabetes is a risk factor for worse outcomes following acute myocardial infarction (AMI). In this study, we tested the hypothesis that SDF-1:CXCR4 expression is compromised in post-AMI in diabetes, and that reversal of this defect can reverse the adverse effects of diabetes. Mesenchymal stem cells (MSC) isolated from ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.17-0172
更新日期:2018-01-01 00:00:00
abstract::Adipose tissue-derived multipotent stromal cells (AT-MSCs) are studied as an alternative to bone marrow-derived multipotent stromal cells (BM-MSCs) for immunomodulatory treatment. In this study, we systematically compared the immunomodulatory capacities of BM-MSCs and AT-MSCs derived from age-matched donors. We found ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2012-0184
更新日期:2013-06-01 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::Human pluripotent stem cells have the potential to promote biological studies and accelerate drug discovery efforts by making possible direct experimentation on a variety of human cell types of interest. However, stem cell cultures are generally heterogeneous and efficient differentiation and purification protocols ar...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.17-0059
更新日期:2017-11-01 00:00:00
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
更新日期:2018-02-01 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::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
更新日期:2012-01-01 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::Mesenchymal stem cells (MSCs) have immunomodulatory properties and support hematopoiesis in the bone marrow (BM). To develop a new strategy not only to prevent graft-vs-host disease (GVHD) but also enhance engraftment, a phase I trial of cord blood transplantation (CBT) combined with intra-BM injection of MSCs (MSC-CB...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.20-0381
更新日期:2020-12-14 00:00:00
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::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::The kidney is a specialized low-regenerative organ with several different types of cellular lineages; however, the identity of renal stem/progenitor cells with nephrogenic potential and their preferred niche(s) are largely unknown and debated. Most of the therapeutic approaches to kidney regeneration are based on admi...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.5966/sctm.2013-0097
更新日期:2013-12-01 00:00:00
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 va...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2014-0101
更新日期:2014-11-01 00:00:00
abstract::Stem cells are promising candidate cells for regenerative applications because they possess high proliferative capacity and the potential to differentiate into other cell types. Mesenchymal stem cells (MSCs) are easily sourced but do not retain their proliferative and multilineage differentiative capabilities after pr...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2013-0079
更新日期:2014-02-01 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