Predicting the Safety and Efficacy of Cell and Tissue Products Used for Repair of Damaged Tissue and Structures through Cell Growth and Maturation Pathways

Principal Investigator: Malcolm Moos, MD, PhD
Office / Division / Lab: OCTGT / DCGT / CTTB

---

Overview

Public Health Issue: Tissues and organs can be damaged by accident, battle trauma, or disease. Improved methods of repair, replacement, or regeneration of damaged tissues and organs are an important public health goal. Novel biological products containing living cells show great promise for use as therapies in these settings, but design, manufacture, and testing of these products has proven very challenging. A major obstacle to successful development has been great uncertainty regarding how best to evaluate experimental cell-based products analytically in order to develop process controls and release specifications that predict product performance reliably.

Regulatory Contribution: To meet this challenge, we identify the biological processes that cells can use to repair damage within the body, and the components that control these processes. This information will help guide sponsors in the development and regulatory approval of novel therapeutic product approaches, lead to improved manufacturing methods, and guide development of laboratory tests that will help ensure consistent, safe, and effective cellular products.

Research Approach: The research program exploits a vertebrate embryology model that is particularly useful for identifying the key biological mechanisms that control repair and regeneration and the interactions between these components. We focus on the medically critical but complicated process of joint development and perform detailed functional analyses of the proteins involved. We have identified several molecules that help control processes such as joint morphogenesis, blood development, and formation of the nervous system. The work has also uncovered ways in which different proteins cooperate to achieve precisely localized control during the formation of complex structures like joints.

Mission Relevance & Outcomes: Some of the molecules we have discovered are being evaluated for therapeutic potential or are being developed as tests for product quality, safety, and efficacy evaluations of cellular products before release for clinical use. Others are being evaluated for their ability to repair or regenerate specific structures, such as joint surfaces, tendons, and ligaments.

---

Publications

Trends Pharmacol Sci 2008 Dec;29(12):591-3
Stem-cell-derived products: an FDA update.
Moos M Jr

J Virol Methods 2008 Nov;153(2):111-9
Establishment of retroviral pseudotypes with influenza hemagglutinins from H1, H3, and H5 subtypes for sensitive and specific detection of neutralizing antibodies.
Wang W, Butler EN, Veguilla V, Vassell R, Thomas JT, Moos M, Ye Z, Hancock K, Weiss CD

Dev Biol 2007 Oct 1;310(1):129-39
Vg1 has specific processing requirements that restrict its action to body axis patterning centers.
Thomas JT, Moos M Jr

J Biol Chem 2006 Sep 8;281(36):26725-33
CDMP1/GDF5 has specific processing requirements that restrict its action to joint surfaces.
Thomas JT, Prakash D, Weih K, Moos M Jr