Optimizing the tracking and the secretome of autologous adipose-derived mesenchymal stromal cells to treat ALS
Ashley Angell Krull, PhD1,4, Nicolas N. Madigan, MB, BCh, BAO, PhD1,4, Nathan P. Staff, MD, PhD1,4, Yasuhiro Ikeda, DVM, PhD2,4, Kah Whye Peng, PhD2,4, Andre J. van Wijnen, PhD3,4, Anthony J. Windebank, MD1,4*,
1Department of Neurology; 2Department of Molecular Medicine; 3Department of Orthopedic Surgery; 4Center for Regenerative Medicine, Mayo Clinic, Rochester, MN
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder involving premature loss of motor neurons in the brain and spinal cord, leading to death within 2-5 years after diagnosis. Despite the prevalence and relentless course of this disorder, no treatments have been developed that can halt or reverse the progression of ALS. Working towards the end of novel therapeutic development, our group identified adipose-derived mesenchymal stromal cells (adMSCs) as a potential therapeutic agent, subsequently completed a Phase I clinical trial in which ALS patients safely tolerated an intrathecal infusion of 108 autologous adMSCs , and now moved into a Phase II clinical trial of adMSC therapy. Through this work, our group has hypothesized that the therapeutic efficacy of patient adMSCs could be enhanced by: 1) tracking the cells in vivo, and 2) enhancing the expression of growth factors by the adMSCs. To track the cells in vivo, our group used Lentiviral vectors to generate adMSCs that express the human sodium-iodide symporter (hNIS), thereby enabling the cells to be tracked via radioisotope imaging. In addition to expressing hNIS, the Lentiviral vector also provides an extra copy of a growth factor gene (e.g., IGF1) that the cell can use to increase expression and secretion of the chosen therapeutic factor. Such advancements in adMSC visualization and utilization as a factory of growth factors will enable physicians to better monitor adMSC viability and efficacy following infusion into each patient. Also, samples of spinal fluid - obtained as part of our clinical trials - could aid in the identification of biomarkers to provide a diagnostic readout of adMSC activity and guide treatment to optimize patient outcomes.
 Staff, N.P., et al. Neurology. 2016;87(21):2230-2234.
T32 Grant for Translational Research in Regenerative Medicine (2T32EB005583)