The Aastrom experience

Ronnda L Bartel,Amy Longcore,Sharon Watling,Frank Zeigler,Christopher Parrish,Kelly Ledford,Caryn Cramer,Theresa Stern

doi:10.1186/scrt117

Ronnda L Bartel, Amy Longcore + Show 6 more

Open Access

https://doi.org/10.1186/scrt117

Copy DOI

Abstract

Aastrom Biosciences has developed a proprietary cell-processing technology that enables the manufacture of ixmyelocel-T, a patient-specific multicellular therapy expanded from a small sample of a patient's own bone marrow. Ixmyelocel-T is produced under current good manufacturing practices (cGMP) in a fully closed, automated system that expands mesenchymal stem cells (MSCs) and macrophages. While the cell types in ixmyelocel-T are the same as those found in the bone marrow, the numbers of MSCs and alternative macrophages are greater in ixmyelocel-T. We propose that the mixture of expanded MSCs and alternatively activated macrophages promote long-term tissue repair of ischemic tissue. The multiple cell types in ixmyelocel-T have a range of biological activities that are likely to contribute to a complex mechanism of action. Clinical trial data collected to date support the potential for ixmyelocel-T as an efficacious and safe treatment for ischemic cardiovascular indications, including critical limb ischemia (CLI) and a severe form of heart failure, dilated cardiomyopathy (DCM). The CLI clinical program has completed phase 2 and has reached concurrence with the Food and Drug Administration (FDA) on a phase 3 study (REVIVE) through the Special Protocol Assessment (SPA) process. The phase 3 study began screening patients in February 2012. The DCM clinical program will initiate phase 2b in 2012.

Highlights

Aastrom Biosciences, founded in 1989, has developed a proprietary cell-processing technology that enables the manufacture of ixmyelocel-T, a patient-specific multicellular therapy expanded from a patient’s own bone marrow
We propose that these activities are the most likely responsible for the complex and multiple mechanisms of action in this multicellular therapy
The product is manufactured using a fully closed, highly automated bioreactor system designed for the ex vivo expansion of autologous marrow-derived stem and progenitor cells that mimics the in vivo environment of bone marrow tissue

Summary

Introduction

Aastrom Biosciences, founded in 1989, has developed a proprietary cell-processing technology that enables the manufacture of ixmyelocel-T, a patient-specific multicellular therapy expanded from a patient’s own bone marrow. Bone marrow maintains a small reservoir of these two cell types that the Aastrom process significantly expands while maintaining many of the mononuclear cells from the original bone marrow sample Not unexpectedly, these diverse cell types display a wide range of biological activities relevant to the repair and regeneration of ischemic tissue, including tissue remodeling and immunomodulation and the promotion of angiogenesis. These diverse cell types display a wide range of biological activities relevant to the repair and regeneration of ischemic tissue, including tissue remodeling and immunomodulation and the promotion of angiogenesis We propose that these activities are the most likely responsible for the complex and multiple mechanisms of action in this multicellular therapy. Summary of the multiplex cytokine analysis of bone marrow mononuclear cells (BMMNCs) compared to ixmyelocel-T CD90+ and CD14+Auto populations.

Conclusions

10. Shireman PK

Findings

15. Goswami V