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 principles of classical molecular drug pharmacokinetics (PK) and pharmacodynamics (PD) to quantitatively understand rate-limiting constraints of cell fate after administration. Future innovations focused on improvements in drug delivery using a PK/PD perspective can aid in designing a cell therapeutic product to overcome any pharmacological barriers for a given disease application. Herein, we present a perspective on the development of an ex vivo mesenchymal stromal therapeutic using a PK/PD framework and also present examples of general cell engineering techniques that implicitly influence the PK/PD curve by genetically modifying cells to regulate their in vivo duration, biodistribution, and activity. Stem Cells Translational Medicine 2019;8:874&879.
journal_name
Stem Cells Transl Medjournal_title
Stem cells translational medicineauthors
Aijaz A,Vaninov N,Allen A,Barcia RN,Parekkadan Bdoi
10.1002/sctm.19-0019subject
Has Abstractpub_date
2019-09-01 00:00:00pages
874-879issue
9eissn
2157-6564issn
2157-6580journal_volume
8pub_type
杂志文章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
更新日期:2021-01-05 00:00:00
abstract::The development of a California-based induced pluripotent stem cell (iPSC) bank based on human leukocyte antigen (HLA) haplotype matching represents a significant challenge and a valuable opportunity for the advancement of regenerative medicine. However, previously published models of iPSC banks have neither addressed...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0052
更新日期:2015-05-01 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::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::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::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::The potential of autologous cell-based therapies including those using multipotent mesenchymal stromal cells (MSCs) is being investigated for multiple sclerosis (MS) and other neurological conditions. However, the phenotype of MSC in neurological diseases has not been fully characterized. We have previously shown that...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.18-0045
更新日期:2018-10-01 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::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::: 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::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
更新日期:2017-09-01 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::Osteoarthritis (OA) remains an intractable clinical challenge. Few drugs are available for reversing this degenerative disease, although some promising candidates have performed well in preclinical studies. Tumor necrosis factor α (TNFα) has been identified as a crucial effector modulating OA pathogenesis. This study ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2014-0200
更新日期:2015-05-01 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::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::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
更新日期:2015-05-01 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::Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persis...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2012-0022
更新日期:2012-11-01 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::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:UNLABELLED:Cell secretion is an important mechanism for stem cell-based therapeutic angiogenesis, along with cell differentiation to vascular endothelial cells or smooth muscle cells. Cell-released microvesicles (MVs) have been recently implicated to play an essential role in intercellular communication. The purpose of...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0177
更新日期:2016-04-01 00:00:00
abstract::Limbal stem cell (LSC) deficiency is a visually debilitating condition caused by abnormal maintenance of LSCs. It is treated by transplantation of donor-derived limbal epithelial cells (LECs), the success of which depends on the presence and quality of LSCs within the transplant. Understanding the immunobiological res...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2016-0175
更新日期:2017-03-01 00:00:00
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
更新日期:2020-12-20 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::Similar to the disease affecting humans, osteoarthritis (OA) is a painful musculoskeletal condition affecting 20% of the adult canine population. Several solutions have been proposed, but the results achieved to date are far from being satisfactory. New approaches, such as intra-articular delivery of cells (including ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,多中心研究
doi:10.1002/sctm.18-0020
更新日期:2018-11-01 00:00:00
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
更新日期:2014-02-01 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::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::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
abstract:UNLABELLED:Studies in hypertension (HTN) pharmacogenomics seek to identify genetic sources of variable antihypertensive drug response. Genetic association studies have detected single-nucleotide polymorphisms (SNPs) that link to drug responses; however, to understand mechanisms underlying how genetic traits alter drug ...
journal_title:Stem cells translational medicine
pub_type: 临床试验,杂志文章
doi:10.5966/sctm.2015-0126
更新日期:2015-12-01 00:00:00