Non-contractile cardiomyocytes for cardiac repair
AssigneeUniversity of Washington
InventorsCharles E. MURRY, Michael REGNIER, Hans REINECKE, Xiulan YANG, Dasom YOO
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Abstract
Described herein are compositions and methods relating to the improvement of cardiac function. Various embodiments relate to transplant compositions comprising cardiomyocytes which are engineered to be non-contractile, and to methods of using such cardiomyocytes or transplant compositions to improve cardiac function, e.g., by administering them to cardiac tissue.
Claims97
A transplant composition comprising a non-contractile cardiomyocyte, wherein the non-contractile cardiomyocyte exhibits impaired excitation-contraction coupling.
The transplant composition of any preceding claim, wherein the non-contractile cardiomyocyte exhibits normal action potentials.
The transplant composition of any preceding claim, wherein the non-contractile cardiomyocyte exhibits normal calcium transients.
The transplant composition of any preceding claim, wherein the non-contractile cardiomyocyte exhibits impaired function of a thin filament.
The transplant composition of any preceding claim, wherein the non-contractile cardiomyocyte is engineered to exhibit impaired function of a thin filament.
The transplant composition of any preceding claim, wherein impaired function of a thin filament comprises impaired calcium binding to troponin.
The transplant composition of any preceding claim, wherein impaired calcium binding to troponin is a result of knockout or mutation of at least one troponin isoform.
The transplant composition of any preceding claim, wherein the non-contractile cardiomyocyte comprises knockout of troponin I (TnI) and/or troponin T (TnT).
The transplant composition of any preceding claim, wherein the non-contractile cardiomyocyte comprises a mutation in troponin C that impairs calcium binding to troponin.
The transplant composition of any preceding claim, wherein the non-contractile cardiomyocyte exhibits impaired actin-myosin binding.
The transplant composition of any preceding claim, wherein the non-contractile cardiomyocyte is engineered to have impaired actin-myosin binding.
The transplant composition of any preceding claim, further comprising a pharmaceutically acceptable carrier.
The transplant composition of any preceding claim, wherein the non-contractile cardiomyocyte is derived from in vitro differentiation of a pluripotent stem cell or a cardiac progenitor cell.
The transplant composition of any preceding claim, wherein the non-contractile cardiomyocyte retains normal gap junction function when contacted with a cardiomyocyte.
A method for improving cardiac function in a subject in need thereof, the method comprising:
- administering a non-contractile cardiomyocyte or a composition thereof to a graft site in cardiac tissue of a recipient in need thereof, thereby improving cardiac function in the subject.
A transplant composition comprising a cardiomyocyte that exhibits attenuated contractility and impaired excitation-contraction coupling.
A transplant composition comprising a cardiomyocyte engineered to have attenuated contractility and/or impaired excitation-contraction coupling.
A method for improving cardiac function in a subject in need thereof, the method comprising:
- administering a cardiomyocyte that exhibits attenuated contractility or a composition thereof to a graft site in cardiac tissue of the subject in need thereof, thereby improving cardiac function in the subject.
A unit dosage formulation comprising non-contractile cardiomyocytes for administration to cardiac tissue of a subject in need thereof, the unit dosage formulation comprising 1×103 to 5×109 non-contractile cardiomyocytes in a gel or matrix.
Dependencies are inferred from the claim text.