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Regenerative Medicine and Immunomodulatory Therapy: Insights From the Kidney, Heart, Brain, and Lung.

ABSTRACT: Regenerative medicine was initially focused on tissue engineering to replace damaged tissues and organs with constructs derived from cells and biomaterials. More recently, this field of inquiry has expanded into exciting areas of translational medicine modulating the body's own endogenous processes, to prevent tissue damage in organs and to repair and regenerate these damaged tissues. This review will focus on recent insights derived from studies in which the manipulation of the innate immunologic system may diminish acute kidney injury and enhance renal repair and recovery without the progression to chronic kidney disease and renal failure. The manner in which these interventions may improve acute and chronic organ dysfunction, including the heart, brain, and lung, will also be reviewed.

SUBMITTER: Pino CJ

PROVIDER: S-EPMC6035130 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Regenerative Medicine and Immunomodulatory Therapy: Insights From the Kidney, Heart, Brain, and Lung.

Pino Christopher J CJ Westover Angela J AJ Johnston Kimberly A KA Buffington Deborah A DA Humes H David HD

Kidney international reports 20180105 4

Regenerative medicine was initially focused on tissue engineering to replace damaged tissues and organs with constructs derived from cells and biomaterials. More recently, this field of inquiry has expanded into exciting areas of translational medicine modulating the body's own endogenous processes, to prevent tissue damage in organs and to repair and regenerate these damaged tissues. This review will focus on recent insights derived from studies in which the manipulation of the innate immunolog ...[more]

PMID: 29989023

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Project description:One of the most complex forms of congenital heart disease (CHD) involving single ventricle physiology is hypoplastic left heart syndrome (HLHS), characterized by underdevelopment of the left ventricle (LV), mitral and aortic valves, and narrowing of the ascending aorta. The underdeveloped LV is incapable of providing long-term systemic flow, and if left untreated, the condition is fatal. Current treatment for this condition consists of three consecutive staged palliative operations: the first is conducted within the first few weeks of birth, the second between 4 to 6 months, and the third and final surgery within the first 4 years. At the conclusion of the third surgery, systemic perfusion is provided by the right ventricle (RV), and deoxygenated blood flows passively to the pulmonary vasculature. Despite these palliative interventions, the RV, which is ill suited to provide long-term systemic perfusion, is prone to eventual failure. In the absence of satisfying curative treatments, stem cell therapy may represent one innovative approach to the management of RV dysfunction in HLHS patients. Several stem cell populations from different tissues (cardiac and non-cardiac), different age groups (adult- vs. neonate-derived), and different donors (autologous vs. allogeneic), are under active investigation. Preclinical trials in small and large animal models have elucidated several mechanisms by which these stem cells affect the injured myocardium, and are driving the shift from a paradigm based upon cellular engraftment and differentiation to one based primarily on paracrine effects. Recent studies have comprehensively evaluated the individual components of the stem cells' secretomes, shedding new light on the intracellular and extracellular pathways at the center of their therapeutic effects. This research has laid the groundwork for clinical application, and there are now several trials of stem cell therapies in pediatric populations that will provide important insights into the value of this therapeutic strategy in the management of HLHS and other forms of CHD. This article reviews the many stem cell types applied to CHD, their preclinical investigation and the mechanisms by which they might affect RV dysfunction in HLHS patients, and finally, the completed and ongoing clinical trials of stem cell therapy in patients with CHD.

Dataset Information

Regenerative Medicine and Immunomodulatory Therapy: Insights From the Kidney, Heart, Brain, and Lung.

Publications

Regenerative Medicine and Immunomodulatory Therapy: Insights From the Kidney, Heart, Brain, and Lung.

Similar Datasets

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