Restoration versus reconstruction: cellular mechanisms of skin, nerve and muscle regeneration compared

Table 2 Kinetics of wound healing of the nerve: main phases and players

	Destruction	Repair	Remodeling
	Days following injury
When	2 to 3 (prolonged up to 7-14)	4 to weeks	8 to weeks
Where	cell body	proximal axon segment	distal axon segment
	injured axon terminal
	distal axonal segment
What	chromatolysis	growth cone sprouting and elongation	nerve remodeling (supernumerary axonal sprout degeneration) reconnection with target (muscle re-innervation)
What	Wallerian degeneration (myelin clearance)	growth cone sprouting and elongation
Who	cell body ⁽¹⁾	Schwann cells ^{(4) (5)}	pericytes ⁽⁷⁾
	B cells, macrophages ⁽²⁾	axons ⁽⁶⁾	Schwann cells ⁽⁸⁾
	Schwann cells ⁽³⁾	axons ⁽⁶⁾	muscle fibers ^{(9) (10)}
How	hypertrophy, protein synthesis⁽¹⁾	NGF ⁽⁴⁾	CNTF ⁽⁷⁾ ⁽⁸⁾
How	immune response ⁽²⁾	BDNF ⁽⁵⁾	IGF-1⁽⁹⁾
	MCP-1, LIF ⁽³⁾	NT-3 and−4/5 ⁽⁶⁾	FGF⁽¹⁰⁾

Following injury, regeneration of the nerve can be schematically divided in three main phases. Complete nerve regeneration in humans depends to a large extent on the length of the gap to be filled and may take many weeks. In addition to the timeline (When), each row indicates the tissue involved (Where), the main output (What), the cell type involved most (Who) and some of the main molecular mediators (How) responsible for the various phases of wound healing. Brain-derived neurotrophic factor (BDNF); ciliary neurotrophic factor (CNTF); fibroblast growth factor (FGF); insulin-like growth factor-1 (IGF-1); leukemia inhibitory factor (LIF); monocyte chemoattractant protein-1 (MCP-1); nerve growth factor (NGF); neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5). Matching superscripts highlight the cells that produce the corresponding growth factors.

ISSN: 2050-490X