Immunophenotypical analyses of myofibroblasts in rat excisional wound healing: possible transdifferentiation of blood vessel pericytes and perifollicular dermal sheath cells into myofibroblasts

Vetnizah Juniantito, Takeshi Izawa, Takahiro Yuasa, Chisa Ichikawa, Emi Yamamoto, Mitsuru Kuwamura and Jyoji Yamate

Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.

Offprint requests to: Jyoji Yamate, DVM, PhD, Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Department of Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Rinkuu Ourai Kita 1-58, Izumisano-shi, Osaka, 598-8531, Japan. e-mail: yamate@vet.osakafu-u.ac.jp


Summary. Cutaneous fibrosis after wound is evoked by myofibroblasts capable of producing collagen; the derivation and features remain to be investigated. Immunophenotypical characteristics of myofibroblasts were analysed in excisional rat wound healing, of which samples were obtained on post-wounding (PW) days 1 to 26. Myofibroblasts were characterized for expressions of intermediate cytoskeletons such as vimentin, desmin, and α-smooth muscle actin (α-SMA). To pursue the progenitor, immunolabeling analyses were performed using stromal-/bone marrow-stem cell markers (Thy-1 and A3). Myofibroblasts reacting to vimentin and α-SMA were first seen on PW day 5, then peaked on PW day 9 in granulation tissues, and gradually decreased in remodeling tissues; these immunopositive cells reacted simultaneously to Thy-1. Desmin-reacting cells were limited to newly-formed blood vessels in wound bed. The single/double immunolabelings revealed that pericytes (identified by positive reaction to PDGFR-ß and negative reaction to endothelial markers) in newly-developing blood vessels reacted to vimentin, α-SMA, Thy-1 and A3, and occasionally to desmin, and that perifollicular dermal sheath cells in the wound periphery showed increased expressions for vimentin, Thy-1 and A3. There is considerable immunophenotypical similarity between myofibroblasts (expressing vimentin, α-SMA and Thy-1), pericytes (reacting to vimentin, α-SMA, Thy-1 and A3) in newly-developing blood vessels, and perifollicular dermal sheath cells (reacting to vimentin, Thy-1 and A3). Collectively, myofibroblasts in rat cutaneous fibrosis are characterized by vimentin, α-SMA and Thy-1 expressions, and the cells might be generated from the pericytes or perifollicular dermal sheath cells in the lineage of stroma-/bone marrow-stem cells. Histol Histopathol 27, 515-527 (2012)

Key words: Wound healing, Myofriboblast, Pericytes, Perifollicular dermal sheath cells

DOI: 10.14670/HH-27.515