Bone marrow-derived cells in the population of spinal microglia after peripheral nerve injury

Area of Science:

• Neuroscience
• Immunology
• Pain Research

Background:

• Peripheral nerve injury (PNI) triggers spinal microglia activation, a key process in neuropathic pain development.
• Previous studies suggested circulating bone marrow (BM)-derived cells infiltrate the spinal cord and become microglia after PNI, implying heterogeneous microglia populations.
• Concerns exist regarding the methodology of BM chimeric mouse models due to irradiation-induced adverse effects.

Purpose of the Study:

• To investigate the contribution of circulating bone marrow-derived cells to the spinal microglia population following peripheral nerve injury.
• To clarify the cellular origins of microglia in the spinal cord after PNI, addressing controversies from previous research.
• To determine if spinal microglia populations are heterogeneous due to bone marrow cell infiltration post-PNI.

Main Methods:

• Utilized irradiation-induced myeloablation with varied conditioning regimens in bone marrow chimeric mice.
• Employed parabiosis models to assess cell migration without irradiation.
• Used genetically labeled microglia mouse models to track endogenous microglia populations.
• Evaluated the spinal infiltration of BM-derived cells post-PNI across these independent models.

Main Results:

• Compelling evidence from multiple, independent experimental approaches demonstrated minimal infiltration of circulating bone marrow-derived cells into the spinal cord after PNI.
• Results from parabiosis and genetically labeled microglia models corroborated findings from BM chimeric mice, even with varied conditioning regimens.
• The study provides strong evidence against a significant contribution of BM-derived cells to the spinal microglia pool post-PNI.

Conclusions:

• Circulating bone marrow-derived cells play a negligible role in the spinal microglia population following peripheral nerve injury.
• The spinal microglia population after PNI is unlikely to be significantly heterogeneous due to the infiltration of bone marrow-derived cells.
• This study refutes previous hypotheses suggesting substantial bone marrow contribution to spinal microglia in the context of neuropathic pain.