Chemoattraction of progenitor cells by remodeling extracellular matrix scaffolds

Abstract

The chemotactic properties of a biologic scaffold composed of extracellular matrix (ECM) and subjected to in vivo degradation and remodeling were evaluated in a mouse model of Achilles tendon reconstruction. Following a segmental resection of the Achilles tendon in both C57BL/6 and MRL/MpJ mice, the defect was repaired with either an ECM scaffold composed of urinary bladder matrix (UBM) or resected autologous tendon. The surgically repaired and the contralateral tendons were harvested at 3, 7, and 14 days following surgery from each animal. Chemotaxis of multipotential progenitor cells toward the harvested tissue was quantified using a fluorescent-based cell migration assay. Results showed greater migration of progenitor cells toward tendons repaired with UBM-ECM scaffold compared to both the tendons repaired with autologous tissue and the normal contralateral tendon in both the MRL/MpJ and C57BL/6 mice. The magnitude and temporal pattern of the chemotactic response differed between the two mouse strains.

FIG. 1.

Schematic diagram illustrating the surgical technique used to transect the Achilles tendon in the autologous repair (AUTO-T) group. (A) Sutures placed prior to segmental excision. (B) Transection between loops of suture creating the autologous tendon repair. (C) Excision of tendon segment with placement of UBM–ECM material.

FIG. 2.

Images showing gene expression in MRL-B cells at passage 14 and tissue controls. RNA was extracted and transcribed, and the subsequent cDNA screened via PCR for Tbx5, MSX-1, DLK, tenascin C, Thy-1, and thrombospondin. All samples tested positive for housekeeping gene GAPDH (data not shown).

FIG. 3.

Graphs showing progenitor cell migration, represented as absorbance, toward tendons excised from C57BL/6 mice (left) and MRL mice (right) 3, 7, and 14 days following surgery for each experimental condition: UBM repair (ECM-T), normal tendon from mouse receiving UBM scaffold (ECM-C), autologous repair (AUTO-T), and normal tendon from the mouse that received the autologous repair (AUTO-C). The results are the mean value (n = 6) ± the standard deviation with asterisk (*) representing p < 0.05.