MSC Therapy Optimization
Clinical applications of MSC-based therapies are reliant on parent MSCs and EVs to successfully migrate to damaged tissues following their administration1. Unfortunately, MSC homing is inefficient with only a small percentage of cells reaching the target tissue following systemic administration2. Indeed, conventional systemic/intravenous administration of MSC-based therapies is rather ineffective given that majority of cells get trapped in the lungs while EVs get trapped in the reticuloendothelial system; this attrition likely represents the major bottleneck from ensuring enough therapy reaches target sites to facilitate tissue regeneration.
Interventional Regenerative Medicine (IRM) is an emerging subspecialty which can be defined by the use of image-guided, minimally-invasive procedures for the targeted delivery of stem cells used in order to regenerate, replace or repair damaged tissues and organs2. IRM aims to deliver cellular therapies directly into affected organs via blood vessels (i.e., endovascular), luminal cavities (i.e., endoluminal) or even directly into the damaged tissue (i.e., intraparanchymal).
In our lab, we have been developing techniques in small animal models to deliver MSC-based therapies directly into organs, such as the pancreas, kidney and brain, via their arterial blood supply in order to enable MSC-based therapies to reach their full therapeutic potential. We have also been investing in the use of pulsed focused ultrasound (pFUS) to modulate and prime the tissue microenvironment to facilitate MSC homing, permeation and retention3.
- Ullah M, Liu DD, Thakor AS (2019). Mesenchymal Stromal Cell Homing: Mechanisms and Strategies for Improvement. iScience, 15, 421–438. PMID: 31121468; PMCID: PMC6529790.
- Ng NN, Thakor AS (2020). Locoregional Delivery of Stem Cell-Based Therapies. Science Translational Medicine, 12(547). PMID: 32522806.
- Liu DD, Ullah M, Concepcion W, Dahl JJ, Thakor AS (2020). The role of ultrasound in enhancing mesenchymal stromal cell-based therapies. Stem cells translational medicine, 10.1002/sctm.19-0391. Advance online publication. PMID: 32157802.