Optimization of targeted cell replacement therapy: a new approach for lung disease.

Molecular Therapy : the Journal of the American Society of Gene Therapy
Pascal DuchesneauThomas K Waddell

Abstract

Cell replacement therapy is a promising approach for treatment of lung disease such as cystic fibrosis, although rates of engraftment need to be improved. We previously showed improved cell retention in the lung using transtracheal delivery compared to intravenous injection. Here, we optimized other parameters of cell delivery using 7-day cultured bone marrow cells (BMCs). Retention of BMC in the lung was dose-dependent. Naphthalene treatment had maximal effects on BMC retention when given 2 days before cell delivery. Naphthalene treatment of the donor amplified a CCSP(+) population and increased retention efficiency in the recipient. Repeated naphthalene treatment and repeated cell delivery both resulted in greater retention. The contribution of the second cell dose was minimal suggesting that a second delivery of BMC promotes proliferation of the first. Busulfan-induced myelosuppression augmented retention of exogenous BMC by up to 20-fold. These BMC helped CCSP reconstitution. Using the optimal delivery techniques and cytokeratin-18-driven green fluorescent protein (GFP) reporter mice, we detected threefold more GFP suggesting more BMC differentiated to epithelial cells. We propose that improved engraftment in the lung will ...Continue Reading

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Citations

Jun 10, 2011·Proceedings of the American Thoracic Society·Daniel J WeissDarwin J Prockop
May 11, 2013·Current Pathobiology Reports·Amy P Wong, Janet Rossant
Apr 12, 2019·Journal of Cellular Physiology·Hamid TebyanianAlexander Seifalian
Mar 30, 2011·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Uta Griesenbach, Eric W F W Alton
Jul 29, 2020·International Journal of Molecular Sciences·Pascal DuchesneauGolnaz Karoubi
Nov 25, 2014·American Journal of Physiology. Lung Cellular and Molecular Physiology·Liqiong GuiLaura E Niklason
Dec 9, 2017·Expert Opinion on Biological Therapy·Massimo ConeseAnnalucia Carbone
May 22, 2020·American Journal of Respiratory Cell and Molecular Biology·Rhianna E LeeScott H Randell

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