Bone marrow derived neurokinin-1 receptor positive (NK1R+) mesenchymal stem cells for therapeutic applications

Inventors

McNiece, IanAltman, Peter

Assignees

Biocardia Inc

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Publication Number

US-11642377-B2

Patent

Publication Date

2023-05-09

Expiration Date


Abstract

The present disclosure provides use of neurokinin 1 receptor (NK1R) as a marker for identifying and/or isolating multipotential cells. The present disclosure provides cell populations enriched by methods of the present disclosure and therapeutic uses of these cells and agents derived from these cells.

Core Innovation

The invention relates to isolating mesenchymal stem cells that express neurokinin-1 receptor (NK1R) from bone marrow of a human subject using an antibody to NK1R, to obtain NK1R+ MSCs for treatment. It further relates to administering therapeutically effective amounts of the NK1R+ MSCs to a patient to treat diseases or disorders selected from cardiovascular disease, pain, rheumatoid arthritis, diabetes, stroke, asthma, pulmonary fibrosis, and aging.

A central aspect of the invention is linking NK1R expression to enrichment and therapeutic use of mesenchymal lineage cells derived from human bone marrow. The described approach includes ex vivo culturing and expansion of NK1R+ MSCs prior to administration, and it is aligned with NK1R biology involving substance P/NK1R.

The invention is described as providing advantages versus cultured MSCs, including logistics and efficacy. It also describes optional enhancements such as culturing in the presence of substance P, using conditioned media, and delivering cells with a biopolymer matrix.

Claims Coverage

Two independent claims are identified: clm-00001 and clm-00016. Across these claims, the inventive features center on isolating NK1R+ MSCs from human bone marrow using an antibody to NK1R, optionally culturing and expanding the NK1R+ MSCs ex vivo, and administering therapeutically effective amounts to treat a specified set of diseases or disorders.

Antibody-based isolation of NK1R+ MSCs from human bone marrow

Isolating mesenchymal stem cells (MSCs) that express neurokinin-1 receptor (NK1R) from a bone marrow of a human subject by using an antibody to NK1R.

Therapeutic administration of NK1R+ MSCs for specified diseases

Administering to a patient a therapeutically effective amount of the NK1R+ MSCs to treat a disease or disorder selected from the set of: cardiovascular disease, pain, rheumatoid arthritis, diabetes, stroke, asthma, pulmonary fibrosis, and aging.

Ex vivo culturing and expansion of NK1R+ MSCs prior to administration

Culturing and expanding the NK1R+ MSCs ex vivo prior to administering the therapeutically effective amount to the patient.

The claim set is directed to treatment methods that depend on obtaining NK1R+ MSCs by antibody-based isolation from human bone marrow, optionally including ex vivo culturing and expansion, followed by administration of therapeutically effective amounts to treat cardiovascular disease, pain, rheumatoid arthritis, diabetes, stroke, asthma, pulmonary fibrosis, and aging.

Stated Advantages

Advantages versus cultured MSCs (logistics and efficacy).

Documented Applications

Treating cardiovascular disease/heart failure including ischemic cardiomyopathy after myocardial infarction.

Treating pain and local inflammatory and autoimmune disorders including rheumatoid arthritis.

Treating stroke.

Treating diabetes.

Treating asthma and pulmonary fibrosis.

Treating aging.

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