Biodistribution of Transplanted Hematopoietic Precursor Cells Injected Through Different Administration Routes in Newborn Mice

Hum Gene Ther. 2021 May;32(9-10):495-505. doi: 10.1089/hum.2019.191. Epub 2021 Apr 16.

Abstract

Hematopoietic stem cell transplantation has been studied for several decades now, mostly as a treatment for malignancies and hematological diseases but also for genetic metabolic disorders. Since many diseases that could be potentially treated with this approach develop early in life, studies of cell transplantation in newborn mice are needed, especially for gene therapy protocols. However, the small size of pups restricts the possibilities for routes of administration, and those available are normally technically challenging. Our goal was to test different routes of administration of Lin- cells in 2-day-old mice: intraperitoneal, intravenous through temporal vein (TV), and intravenous through retro-orbital (RO) sinus. Routes were evaluated by their easiness of execution and their influence in the biodistribution of cells in the short (48 h) and medium (30 days) term. In either 48 h or 30 days, all three routes presented similar results, with cells going mostly to bone marrow, liver, and spleen in roughly the same number. RO injection resulted in quick distribution of cells to the brain, suggesting better performance than the others. Rate of failure was higher for the TV route, which was also the hardest to execute, whereas the other two were considered easier. In conclusion, TV was the hardest to perform and all routes seemed to demonstrate similar results for cell biodistribution. In particular, the RO injection results in quicker biodistribution of cells to the brain, which is particularly important in the study of genetic metabolic disorders with a neurological component.

Keywords: administration routes; hematopoietic stem cells; intraperitoneal; newborn; retro-orbital; temporal vein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Hematopoietic Stem Cell Transplantation*
  • Liver / metabolism
  • Mice
  • Spleen
  • Tissue Distribution