Cardiac stem cells for cardiac repair
Inventors
Assignees
University of Maryland Baltimore
Publication Number
US-12220432-B2
Publication Date
2025-02-11
Expiration Date
2035-05-14
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Abstract
Embodiments of the disclosure concern compositions and methods of use related to particular c-kit+ mesenchymal cells, including cardiac stem cells, obtained from a pediatric or neonatal individual. In specific embodiments, the cells, or conditioned medium or partial or total secretomes thereof, are provided in an effective amount to an individual in need thereof.
Core Innovation
The invention concerns compositions and methods using c-kit+ mesenchymal cells, including specific cardiac stem cells, obtained from neonatal or pediatric individuals for the treatment of cardiac medical conditions. These cells, or their conditioned medium or secretome (including exosomes), are provided to individuals in need of cardiac regenerative or remodeling therapy. The patent describes the isolation, characterization, and application of these c-kit+ cardiac stem cells, including their use as a pharmaceutical composition in an effective amount for therapeutic benefit.
The problem addressed by the invention is the need for effective compositions and methods to regenerate functional myocardium in adults and children with cardiac medical conditions, such as heart failure caused by damaged myocardial tissue. Existing therapies have limited efficacy in promoting myocardial regeneration or remodeling, especially in the context of pediatric or neonatal conditions where congenital defects or heart failure present significant challenges.
By providing human neonatal c-kit+ cardiac stem cells with defined markers and secretory profiles, the invention introduces cell-based compositions and related products (such as conditioned media and exosomes) that enhance cardiac regeneration or remodeling. The cells are characterized by specific positive and negative protein markers, including high expression of c-kit, SDF-1α, VEGF-A, PDGF-B, IL-6, FGF-2, and Nkx2.5, and are negative for ISL1 as well as several other surface proteins. These compositions are aimed at facilitating functional recovery in damaged myocardium through direct administration or through paracrine actions mediated by their secretome.
Claims Coverage
The independent claim provides the main inventive features of a pharmaceutical composition comprising specific neonatal human cardiac stem cells with distinct protein expression profiles, combined with a pharmaceutically acceptable carrier.
Pharmaceutical composition comprising human, neonatal cardiac stem cells with defined protein expression profile
The pharmaceutical composition contains human, neonatal cardiac stem cells and a pharmaceutically acceptable carrier, where the human, neonatal cardiac stem cells: - Are positive for protein expression of ckit, SDF-1α, VEGF-A, PDGF-B, IL-6, FGF-2, and Nkx2.5 - Are negative for protein expression of ISL1 - Are negative for protein expression of CD31, CD106, CD140b, or CD86
The claim coverage centers on a pharmaceutical composition containing human, neonatal cardiac stem cells defined by a combination of positive and negative protein expression markers, for use in treating cardiac conditions.
Stated Advantages
The human neonatal c-kit+ cardiac stem cells exhibit strong regenerative ability, improving cardiac function and inducing remodeling of damaged myocardium.
Conditioned medium and exosomes derived from neonatal c-kit+ cells induce functional recovery and promote neovascularization in infarcted myocardium.
Neonatal c-kit+ cardiac stem cells can serve as an “off the shelf” immunologically privileged stem cell product for allogeneic transplantation.
The secretome, including exosomes, of these cells contains pro-angiogenic, pro-proliferative, and anti-apoptotic factors that improve cardiac function and attenuate ventricular remodeling.
Documented Applications
Treatment of cardiac medical conditions, specifically including heart failure, cardiomyopathy, and congenital heart disease.
Use in promoting myocardial regeneration, reversing established cardiac medical conditions such as cardiomyopathy or congestive heart failure, and preventing ventricular remodeling.
Therapy for cardiac conditions in pediatric and neonatal patients with damaged myocardium, including application in patients with end stage heart failure or congenital heart disease.
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