Cell Therapy in Kidney Disease: Cautious Optimism … But Optimism Nonetheless

2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 94-103
Author(s):  
Andrey G. Zenovich ◽  
Doris A. Taylor
Keyword(s):  
Renal Failure ◽  
Kidney Disease ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Therapeutic Potential ◽  
Lessons Learned ◽  
Regulatory Function ◽  
Original Research ◽  
Cell Therapies

The recently discovered therapeutic potential of stem or progenitor cells has initiated development of novel treatments in a number of diseases—treatments that could not only improve patients’ quality of life, but also halt or even prevent disease progression. Hypertension; fluctuations in glycemia, electrolytes, nutrient levels, and circulating volume; and frequent infections and the associated inflammation all greatly impair the endothelium in patients undergoing peritoneal dialysis. As our understanding of the regulatory function of the endothelium advances, focus is increasingly being placed on endothelial repair in acute and chronic renal failure and after renal transplantation. The potential of progenitor cells to repair damaged endothelium and to reduce inflammation in patients with renal failure remains unexamined; however, a successful cell therapy could reduce morbidity and mortality in kidney disease. Important contributions have been made in identifying progenitor cell populations in the kidney, and further investigations into the relationships of these cells with the pathophysiology of the disease are underway. As the kidney disease field prepares for the first human trials of progenitor cell therapies, we deemed it important to review representative original research, and to share our perspectives and lessons learned from clinical trials of progenitor cell–based therapies that have commenced in patients with cardiovascular disease.

scholarly journals Progenitor Cell Therapy for the Treatment of Central Nervous System Injury: A Review of the State of Current Clinical Trials

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Peter A. Walker ◽  
Matthew T. Harting ◽  
Shinil K. Shah ◽  
Mary-Clare Day ◽  
Ramy El Khoury ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Progenitor Cell ◽  
Neurological Injury ◽  
Cell Therapies ◽  
Potential Efficacy ◽  
Cord Injury

Recent preclinical work investigating the role of progenitor cell therapies for central nervous system (CNS) injuries has shown potential neuroprotection in the setting of traumatic brain injury (TBI), spinal cord injury (SCI), and ischemic stroke. Mechanisms currently under investigation include engraftment and transdifferentiation, modulation of the locoregional inflammatory milieu, and modulation of the systemic immunologic/inflammatory response. While the exact mechanism of action remains controversial, the growing amount of preclinical data demonstrating the potential benefit associated with progenitor cell therapy for neurological injury warrants the development of well-controlled clinical trials to investigate therapeutic safety and efficacy. In this paper, we review the currently active or recently completed clinical trials investigating the safety and potential efficacy of bone marrow-derived progenitor cell therapies for the treatment of TBI, SCI, and ischemic stroke. Our review of the literature shows that while the preliminary clinical trials reviewed in this paper offer novel data supporting the potential efficacy of stem/progenitor cell therapies for CNS injury, a great deal of additional work is needed to ensure the safety, efficacy, and mechanisms of progenitor cell therapy prior to widespread clinical trials.

scholarly journals Tissue Engineering Approaches for Enamel, Dentin, and Pulp Regeneration: An Update

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Geraldine M. Ahmed ◽  
Eman A. Abouauf ◽  
Nermeen AbuBakr ◽  
Christof E. Dörfer ◽  
Karim Fawzy El-Sayed
Keyword(s):  
Cell Therapy ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Clinical Applications ◽  
Multilineage Differentiation ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Dental Tissues ◽  
Undifferentiated Cells ◽  
Different Sources

Stem/progenitor cells are undifferentiated cells characterized by their exclusive ability for self-renewal and multilineage differentiation potential. In recent years, researchers and investigations explored the prospect of employing stem/progenitor cell therapy in regenerative medicine, especially stem/progenitor cells originating from the oral tissues. In this context, the regeneration of the lost dental tissues including enamel, dentin, and the dental pulp are pivotal targets for stem/progenitor cell therapy. The present review elaborates on the different sources of stem/progenitor cells and their potential clinical applications to regenerate enamel, dentin, and the dental pulpal tissues.

Activation of Epac stimulates integrin-dependent homing of progenitor cells

Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2640-2646 ◽  
Author(s):  
Guillaume Carmona ◽  
Emmanouil Chavakis ◽  
Ulrike Koehl ◽  
Andreas M. Zeiher ◽  
Stefanie Dimmeler
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Matrix Protein ◽  
Therapeutic Potential ◽  
Limb Ischemia ◽  
Β1 Integrin ◽  
Nucleotide Exchange ◽  
Β2 Integrin ◽  
The Matrix

Cell therapy is a novel promising option for treatment of ischemic diseases. Administered endothelial progenitor cells (EPCs) are recruited to ischemic regions and improve neovascularization. However, the number of cells that home to ischemic tissues is restricted. The GTPase Rap1 plays an important role in the regulation of adhesion and chemotaxis. We investigated whether pharmacologic activation of Epac1, a nucleotide exchange protein for Rap1, which is directly activated by cAMP, can improve the adhesive and migratory capacity of distinct progenitor cell populations. Stimulation of Epac by a cAMP-analog increased Rap1 activity and stimulated the adhesion of human EPCs, CD34+ hematopoietic progenitor cells, and mesenchymal stem cells (MSCs). Specifically, short-term stimulation with a specific Epac activator increased the β2-integrin–dependent adhesion of EPCs to endothelial cell monolayers, and of EPC and CD34+ cells to ICAM-1. Furthermore, the Epac activator enhanced the β1-integrin–dependent adhesion of EPCs and MSCs to the matrix protein fibronectin. In addition, Epac1 activation induced the β1- and β2-integrin–dependent migration of EPCs on fibronectin and fibrinogen. Interestingly, activation of Epac rapidly increased lateral mobility of β1- and β2-integrins, thereby inducing integrin polarization, and stimulated β1-integrin affinity, whereas the β2-integrin affinity was not increased. Furthermore, prestimulation of EPCs with the Epac activator increased homing to ischemic muscles and neovascularization-promoting capacity of intravenously injected EPCs in the model of hind limb ischemia. These data demonstrate that activation of Epac1 increases integrin activity and integrin-dependent homing functions of progenitor cells and enhances their in vivo therapeutic potential. These results may provide a platform for the development of novel therapeutic approaches to improve progenitor cell homing.

scholarly journals State of the Art Review of Cell Therapy in the Treatment of Lung Disease, and the Potential for Aerosol Delivery

2020 ◽  
Vol 21 (17) ◽  
pp. 6435
Author(s):  
Hosanna Brave ◽  
Ronan MacLoughlin
Keyword(s):  
Cell Therapy ◽  
Therapeutic Potential ◽  
State Of The Art ◽  
Primary Objective ◽  
Pulmonary Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Cell Therapies ◽  
Routes Of Administration ◽  
Advanced Therapy

Respiratory and pulmonary diseases are among the leading causes of death globally. Despite tremendous advancements, there are no effective pharmacological therapies capable of curing diseases such as COPD (chronic obstructive pulmonary disease), ARDS (acute respiratory distress syndrome), and COVID-19. Novel and innovative therapies such as advanced therapy medicinal products (ATMPs) are still in early development. However, they have exhibited significant potential preclinically and clinically. There are several longitudinal studies published, primarily focusing on the use of cell therapies for respiratory diseases due to their anti-inflammatory and reparative properties, thereby hinting that they have the capability of reducing mortality and improving the quality of life for patients. The primary objective of this paper is to set out a state of the art review on the use of aerosolized MSCs and their potential to treat these incurable diseases. This review will examine selected respiratory and pulmonary diseases, present an overview of the therapeutic potential of cell therapy and finally provide insight into potential routes of administration, with a focus on aerosol-mediated ATMP delivery.

scholarly journals Effects of nicotine on the translation of stem cell therapy

2020 ◽  
Vol 15 (5) ◽  
pp. 1679-1688
Author(s):  
Alex HP Chan ◽  
Ngan F Huang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Therapeutic Potential ◽  
Electronic Cigarettes ◽  
Nicotine Exposure ◽  
Cell Therapies ◽  
Lifestyle Choices

Although stem cell therapy has tremendous therapeutic potential, clinical translation of stem cell therapy has yet to be fully realized. Recently, patient comorbidities and lifestyle choices have emerged to be important factors in the efficacy of stem cell therapy. Tobacco usage is an important risk factor for numerous diseases, and nicotine exposure specifically has become increasing more prevalent with the rising use of electronic cigarettes. This review describes the effects of nicotine exposure on the function of various stem cells. We place emphasis on the differential effects of nicotine exposure in vitro and as well as in preclinical models. Further research on the effects of nicotine on stem cells will deepen our understanding of how lifestyle choices can impact the outcome of stem cell therapies.

The use of hydrogels for cell-based treatment of chronic kidney disease

2018 ◽  
Vol 132 (17) ◽  
pp. 1977-1994 ◽  
Author(s):  
Meg L. McFetridge ◽  
Mark P. Del Borgo ◽  
Marie-Isabel Aguilar ◽  
Sharon D. Ricardo
Keyword(s):  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Stem Cell ◽  
Kidney Disease ◽  
Cell Therapy ◽  
Delivery System ◽  
Stem Cell Therapy ◽  
Therapeutic Potential ◽  
Health Concern ◽  
Paracrine Effects

Chronic kidney disease (CKD) is a major and growing public health concern with increasing incidence and prevalence worldwide. The therapeutic potential of stem cell therapy, including mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) holds great promise for treatment of CKD. However, there are significant bottlenecks in the clinical translation due to the reduced number of transplanted cells and the duration of their presence at the site of tissue damage. Bioengineered hydrogels may provide a route of cell delivery to enhance treatment efficacy and optimise the targeting effectiveness while minimising any loss of cell function. In this review, we highlight the advances in stem cell therapy targeting kidney disease and discuss the emerging role of hydrogel delivery systems to fully realise the potential of adult stem cells as a regenerative therapy for CKD in humans. MSCs and EPCs mediate kidney repair through distinct paracrine effects. As a delivery system, hydrogels can prolong these paracrine effects by improving retention at the site of injury and protecting the transplanted cells from the harsh inflammatory microenvironment. We also discuss the features of a hydrogel, which may be tuned to optimise the therapeutic potential of encapsulated stem cells, including cell-adhesive epitopes, material stiffness, nanotopography, modes of gelation and degradation and the inclusion of bioactive molecules. This review concludes with a discussion of the challenges to be met for the widespread clinical use of hydrogel delivery system of stem cell therapy for CKD.

scholarly journals STEM CELLS: AN APPROACH FOR TREATMENT OF ATHEROSCLEROSIS

2018 ◽  
Vol 11 (10) ◽  
pp. 55
Author(s):  
Vinod Kumar Jatav ◽  
Sunita Sharma
Keyword(s):  
Stem Cells ◽  
Smooth Muscle ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Vascular Remodeling ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Adult Stem Cell ◽  
Cell Therapies ◽  
Atherosclerosis Progression

The contribution of stem cells to control atherosclerosis progression and vascular remodeling after injury in humans is established; however, many details are still unknown. The success with stem cell therapies in the treatment of hematological disorders over the past four decades enhanced our understanding of the physiology of vascular remodeling and motivated towards regenerative medicine and therapeutic restoration of the damaged organ. Stem cells isolated from bone marrow are currently being tested for their therapeutic potential in a variety of clinical conditions including cardiovascular injury, kidney failure, cancer, neurological, and bone disorders. The main focus of this review paper is to reveal the role of different types of stem cells such as embryonic stem cell, adult stem cell, smooth muscle progenitor cells, endothelial progenitor cells, mesenchymal stem cells, and vascular smooth muscle cells and find out possibility to use them for the treatment of atherosclerosis as well as to reduce atheroma formation.

scholarly journals Epicardial Transplantation of Cardiac Progenitor Cells Based Cells Sheets is More Promising Method for Stimulation of Myocardial Regeneration, Than Conventional Cell Injections

Kardiologiia ◽  
2019 ◽  
Vol 59 (5) ◽  
pp. 53-60 ◽  
Author(s):  
K. V. Dergilev ◽  
Z. I. Tsokolayeva ◽  
I. B. Beloglazova ◽  
E. I. Ratner ◽  
E. V. Parfyonova
Keyword(s):  
Progenitor Cells ◽  
Cardiac Remodeling ◽  
Progenitor Cell ◽  
Therapeutic Potential ◽  
Heart Diseases ◽  
Cardiac Progenitor Cells ◽  
Cell Sheets ◽  
Intramyocardial Delivery ◽  
Conventional Cell ◽  
Stimulation Of

Today, transplantation of stem / progenitor cells is a promising approach for the treatment of heart diseases. The therapeutic potential of transplanted cells directly depends on the method of delivery to the myocardium, which determines their regenerative properties. It is important for the development of effective methods of cell therapy. In this paper, we performed a comparative study of efficacy of cardiac progenitor cell (CPC) transplantation by intramyocardial needle injections and by tissue engineering constructs (TEC) – “cell sheets” consisting of cells and their extracellular matrix. It has been shown, that transplantation of TEC in comparison with the intramyocardial delivery provides more extensive distribution and retains more proliferating cellular elements in the damaged myocardium, attenuates the negative cardiac remodeling of the left ventricle and promotes its vascularization.   

scholarly journals Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease 

2020 ◽  
Author(s):  
Patrícia de Carvalho Ribeiro ◽  
Fernando Henrique Lojudice ◽  
Ida Maria Maximina Fernandes-Charpiot ◽  
Maria Alice Sperto Ferreira Baptista ◽  
Stanley de Almeida Araújo ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Kidney Disease ◽  
Cell Therapy ◽  
Induced Pluripotent Stem Cells ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Renal Progenitor Cells ◽  
Induced Pluripotent ◽  
Renal Progenitor

Abstract BackgroundChronic Kidney Disease (CKD) is a global public health problem. Cell therapy using pluripotent stem cells represents an attractive therapeutic approach for the treatment of CKD.MethodsWe transplanted Mitomycin C (MMC)-treated human induced pluripotent stem cells (hiPSCs) and renal progenitor cells (RPCs) into a CKD rat model system. The RPCs and hiPSCs cells were characterized by immunofluorescence and qRT-PCR. Untreated 5/6 nephrectomized rats were compared to CKD animals receiving the same amount of MMC-treated hiPSCs or RPCs. Renal function, histology and immunohistochemistry were evaluated 45 days post-surgery. ResultsWe successfully generated hiPSCs from peripheral blood and differentiated them into RPCs expressing renal progenitor genes (PAX2, WT1, SIX2, and SALL1) and podocyte-related genes (SYNPO, NPHS1). RPCs also exhibited reduced OCT4 expression, confirming the loss of pluripotency. After cell transplantation into CKD rats, the body weight change was significantly increased in both hiPSC and RPC groups, in comparison with the control group. Creatinine clearance (CCr) was preserved only in the hiPSC group. Similarly, the number of macrophages in the kidneys of the hiPSC group reached a statistically significant reduction, when compared to control rats. Both treatments reduced positive staining for the marker α-smooth muscle actin. Histological features showed decreased tubulointerstitial damage (interstitial fibrosis and tubular atrophy) as well as a reduction in glomerulosclerosis in both iPSC and RPC groups.ConclusionsIn conclusion, we describe that both MMC-treated hiPSCs and RPCs exert beneficial effects in attenuating CKD progression. Both cell types were equally efficient to reduce histological damage and weight loss caused by CKD. hiPSCs seems to be more efficient than RPCs, possibly due to a paracrine effect triggered by hiPSCs. These results demonstrate that the use of MMC-treated hiPSCs and RPCs improve clinical and histological CKD parameters, avoided tumor formation, and therefore may be a promising cell therapy strategy for CKD.

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