Compositions and methods for tissue engineering and cell based therapies

US9682078B2 · kind B2 · utility

Assignee

• University of Virginia Patent Foundation · US

Inventors

• Edward A. Botchwey, III · Decatur, US
• Mary Laughlin · Crozet, US
• Kevin R. Lynch · Charlottesville, US
• Anusuya Das · Charlottesville, US
• Anthony Awojoodu · Burtonsville, US

Key dates

• Filing date: Mar 16, 2012
• Grant date: Jun 20, 2017
• Expiry date: Jun 1, 2033

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P17/02
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present application discloses strategies to recruit and mobilize stem cells using S1P receptor selective agonists and antagonists as wells as regulators of chemokine receptors. In an in vivo ischemic model, S1P1/S1P3 activation with FTY720 impeded inflammatory cell infiltration and recruited endothelial progenitor cells (EPCs) with the potential to increase microvascular remodeling. S1P3 expression on marrow-derived cells was essential for this remodeling. Concurrent systemic S1P3 and CXCR4 antagonism mobilized hematopoietic stem cells (HSCs) with the ability to engraft and repopulate blood cells. Pre-treatment of donor HSCs with FTY720 increased homing toward SDF-1 and improved engraftment in marrow. FTY720-coated bone allografts coupled with systemic administration of VPC01091 enhanced bone allograft integration and new bone formation in bone defects. MSCs pre-treated with FTY720 exhibited increased migration toward SDF-1, a CXCR4+ ligand. The results show that S1P is a very powerful role player in pharmacological marrow-derived stem cell mobilization and recruitment.