Lnk deletion reinforces the function of bone marrow progenitors in promoting neovascularization and astrogliosis following spinal cord injury

Stem Cells. 2010 Feb;28(2):365-75. doi: 10.1002/stem.243.

Abstract

Lnk is an intracellular adaptor protein reported as a negative regulator of proliferation in c-Kit positive, Sca-1 positive, lineage marker-negative (KSL) bone marrow cells. The KSL fraction in mouse bone marrow is believed to represent a population of hematopoietic and endothelial progenitor cells (EPCs). We report here that, in vitro, Lnk(-/-) KSL cells form more EPC colonies than Lnk(+/+) KSL cells and show higher expression levels of endothelial marker genes, including CD105, CD144, Tie-1, and Tie2, than their wild-type counterparts. In vivo, the administration of Lnk(+/+) KSL cells to a mouse spinal cord injury model promoted angiogenesis, astrogliosis, axon growth, and functional recovery following injury, with Lnk(-/-) KSL being significantly more effective in inducing and promoting these regenerative events. At day 3 following injury, large vessels could be observed in spinal cords treated with KSL cells, and reactive astrocytes were found to have migrated along these large vessels. We could further show that the enhancement of astrogliosis appears to be caused in conjunction with the acceleration of angiogenesis. These findings suggest that Lnk deletion reinforces the commitment of KSL cells to EPCs, promoting subsequent repair of injured spinal cord through the acceleration of angiogenesis and astrogliosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism
  • Astrocytes / physiology*
  • Bone Marrow Cells / cytology*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / physiology*
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Neovascularization, Physiologic / genetics
  • Neovascularization, Physiologic / physiology*
  • Proteins / genetics
  • Proteins / physiology*
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / physiopathology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • Lnk protein, mouse
  • Membrane Proteins
  • Proteins