Chemokine upregulation in response to anal sphincter and pudendal nerve injury: potential signals for stem cell homing.

PURPOSE

Stromal derived factor-1 (SDF-1) and monocyte chemotactic protein-3 (MCP-3) are signals forcing the migration of bone marrow-derived stem cells to ischemic tissue. This study investigates SDF-1 and MCP-3 expression following direct injury to the anal sphincter and pudendal nerve and to determine if these same mechanisms have any role.

METHODS

Chemokine expression was studied after anal sphincter injury in female rats after either a sphincterotomy (n = 15), pudendal nerve crush (PNC; n = 15), sham pudendal nerve crush (n = 15), or acted as unmanipulated controls (n = 5). Analysis was done at 1 h and 10 and 21 days after injury.

RESULTS

After injury, SDF-1 expression increased 40.2 ± 6.42 (P = 0.01) at 1 h and 28.2 ± 2.37 (P = 0.01) at 10 days, respectively, compared to controls. Likewise, MCP-3 expression increased 40.8 ± 8.17 (P = 0.02) at the same intervals compared to controls. After PNC, SDF-1 expression increased 46.4 ± 6.01 (P = 0.02) and 50.6 ± 10.11 (P = 0.01), and MCP-3 expression increased 46.3 ± 7.76 (P = 0.03) and 190.8 ± 22.15 (P = 0.01), respectively, at the same time intervals compared to controls. However, when PNC was compared to sham injured, a significant increase was seen in SDF-1 and MCP-3 at 10 days. At 21 days, PNC compared to sham injured was significantly low in expression for both SDF-1 and MCP-3 (P < 0.05).

CONCLUSIONS

Direct anal sphincter injury results in higher levels of SDF-1 and MCP-3 expression soon after injury, whereas denervation via pudendal nerve crush results in greater SDF-1 and MCP-3 expression 10 days after injury. Chemokine overexpression suggests the potential for cell-based therapeutic strategies.