Leland Stanford Junior University

Siemens Healthcare Diagnostics Products Gmbh

Sanofi-a Ventis Deutschland Gmbh

Dornier Medtech Systems, Gmbh

T2cure Gmbh

Christopher Heeschen

John P Cooke

James Jang

Andreas Michael Zeiher

Stefanie Dimmeler

Phillip Tsao

Michael Weis

Frances Lauri Johnson

Anjali Pathak

Philip S Tsao

Christian Hamm

Harald Eizenhofer

Andreas Lutz

Hartmut Ruetten

Alexandra Aicher

Improving cell therapy and tissue regeneration in a patient suffering from a cardiovascular or a neurological disease by treating a tissue of the patient with shock waves and/or applying to the patient a therapeutically effective amount of stem cells and/or progenitor cells. Such treatment increases expression of chemoattractants, pro-angiogenic factors, and pro-survival factors. The chemoattractants can be, for example, vascular endothelial growth factor (VEGF) or stromal cell derived factor 1 (SDF-1). For example, the treated tissue can be located in the patient's heart or in a skeletal muscle of the patient, and the shock waves can be extracorporeal shock waves (ESW) or intracorporeal shock waves. The cardiovascular disease can have an ischemic or non-ischemic etiology. For example, the cardiovascular disease can be a myocardial infarction, ischemic cardiomyopathy, or a dilatative cardiomyopathy. For example, the neurological disease can be a peripheral neuropathy or neuropathic pain.

Methods for improving cell therapy and tissue regeneration in patients with cardiovascular diseases by means of shockwaves

The invention relates to novel markers of vascular inflammation and combinations thereof as diagnostic and prognostic tools in patients with cardiovascular diseases. The markers also act as tools that facilitate the selection of active ingredients for the treatment of such diseases, and finally act as starting points for the treatment of cardiovascular diseases. Furthermore, the invention relates to the creation of an individual risk profile of negative events that are associated with the progression of arteriosclerosis.

sCD40L and placental growth factor (PLGF) as biochemical marker combinations in cardiovascular diseases

sCD40L and placental growth factor (PLGF) used as a biochemical marker combination in cardiovascular diseases

The present invention relates to the use of compounds which enhance the transcription of endothelial nitric oxide synthase (eNOS) for treating stem and progenitor cells in the cell therapy of patients with ischemic heart diseases such as coronary heart disease or ischemic cardiomyopathy. Treatment of such cells which are isolated from bone marrow, for example, with an eNOS transcription enhancer prior to their administration improves their functional activity and ameliorates neovascularization of the heart and cardiac regeneration.

Use of eNOS transcription enhancers in the cell therapy of ischemic heart diseases

The present invention features methods for induction of angiogenesis by administration of nicotine or other nicotine receptor agonist. Induction of angiogenesis by the methods of the invention can be used in therapeutic angiogenesis in, for example, treatment of ischemic syndromes such as coronary or peripheral arterial disease.

Nicotine in therapeutic angiogenesis and vasculogenesis

The present invention features methods for recruitment of bone marrow-derived stem cells (e.g., endothelial cell precursors, hematopoietic stem cells) by administration of nicotine or other nicotine receptor agonist. The methods of the invention can be used in, for example, treatment of conditions amenable to treatment by recruitment of bone marrow-derived stem cells (e.g., neutropenia).

Nicotine receptor agonists in stem cell and progenitor cell recruitment

The present invention relates to an in vitro method for the analysis of a sample from a mammal in connection with cardiovascular diseases, wherein the method comprises the following steps: a) isolating of bone marrow-precursor cells (BMPs) and/or blood-derived circulating precursor cells (BDPs) by means of cell specific surface markers, and b) detecting the cardiovascular functionality of the isolated BMPs and/or BDPs by means of a suitable migration assay. The method according to the invention can be employed as a kit in the context of the diagnosis and/or the prognosis of cardiovascular diseases, for the monitoring of their therapies and/or for a stratification for a prospective cell therapy with stem- and/or precursor cells in order to increase the perfusion of ischemic tissue or for a regeneration of tissue losses (e.g. heart insufficiency), respectively. In a further aspect, the present invention then relates to an in vitro method for isolating specific bone marrow-precursor cells by means of a suitable migration assay. According to the invention, these BMPs and/or BDPs can be used for the treatment of cardiovascular diseases, selected from the group consisting of stable coronary heart disease, acute coronary syndrome, acute myocardial infarction, chronic ischemic cardiomyopathy (ICMP), dilatative cardiomyopathy (DCM) or other causes for a heart insufficiency.

In vitro method for the diagnosis of cardiovascular functionality of bone marrow precursor cells (BMPS) and/or blood-derived circulating precursor cells (BDPS)

The present invention provides methods of reducing angiogenesis in an individual. The methods generally involve administering to the individual an effective amount of a nicotinic acetyl choline receptor antagonist. The methods are useful to treat conditions associated with or resulting from angiogenesis, particularly pathological angiogenesis. The invention further provides methods of treating a condition associated with or resulting from angiogenesis.

Methods of reducing angiogenesis

Methods are provided for induction of angiogenesis by administration of nicotine or other nicotine receptor agonist. Induction of angiogenesis by the methods of the invention can be used in therapeutic angiogenesis in, for example, treatment of ischemic syndromes such as coronary or peripheral arterial disease.

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Menlo Park, CA, United States of America

Christopher Heeschen