Treatment of Orthopaedic Infections using Activated Adult Mesenchymal Stem Cells
Technical Report,10 Apr 2015,31 Dec 2019
University of Pittsburgh Pittsburgh United States
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In this application, we propose the patients own stem cells as a promising, autologous cell type for sustained local delivery of antimicrobial peptides, for use as an adjunct therapeutic for orthopaedic infections. Rationale Adult mesenchymal stem cells MSCs can be easily isolated from various adult tissue sources such as bone marrow, adipose, bone and muscle, and retain their differentiation potential during in vitro culture expansion and manipulation. Recent studies have focused on adipose tissue-derived stromalstem cells ASCs because they are easily isolated in numbers 100- to 2,500-fold greater than bone marrow-derived stem cells, for example, while possessing the ability to differentiate into many tissue and regulate immune responses. ASCs secrete many therapeutic cytokines that are anti-inflammatory and control immune responses. Of particular relevance to this proposal, MSCs have recently been shown to secrete antimicrobial peptides AMPs that act against a variety of bacteria. The benefits of AMPs over current treatments are that they do not induce antibiotic resistance and they selectively act against bacteria without negatively impacting the patients tissues. The production of these AMPs is induced by exposure to bacterial products such as lipopolysaccharide LPS, a component of bacterial cell walls. LL-37, a cleavage product of the protein Cathelicidin, is a major AMP produced by MSCs. LL-37 is antimicrobial and prevents the formation of biofilms that bacteria produce to protect themselves from a patients immune system.
- Anatomy and Physiology
- Medicine and Medical Research