Delivery strategies for cell-based therapies in the brain: overcoming multiple barriers

Drug Deliv Transl Res. 2021 Dec;11(6):2448-2467. doi: 10.1007/s13346-021-01079-1. Epub 2021 Oct 30.

Abstract

Cell-based therapies to the brain are promising for the treatment of multiple brain disorders including neurodegeneration and cancers. In order to access the brain parenchyma, there are multiple physiological barriers that must be overcome depending on the route of delivery. Specifically, the blood-brain barrier has been a major difficulty in drug delivery for decades, and it still presents a challenge for the delivery of therapeutic cells. Other barriers, including the blood-cerebrospinal fluid barrier and lymphatic-brain barrier, are less explored, but may offer specific challenges or opportunities for therapeutic delivery. Here we discuss the barriers to the brain and the strategies currently in place to deliver cell-based therapies, including engineered T cells, dendritic cells, and stem cells, to treat diseases. With a particular focus on cancers, we also highlight the current ongoing clinical trials that use cell-based therapies to treat disease, many of which show promise at treating some of the deadliest illnesses.

Keywords: Blood–brain barrier; Brain; Cancer; Drug delivery; Neural stem cells; T cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biological Transport / physiology
  • Blood-Brain Barrier*
  • Brain
  • Brain Diseases* / therapy
  • Drug Delivery Systems
  • Humans