Stem Cells Isolated from the Sheath and Core Tissues of Human Plantar Fascia Exhibit Differential Biological Properties

Abstract

Category: Hindfoot Introduction/Purpose: Plantar fasciitis is a very common ligament disease which affects more than 3 million patients in the United States every year. However, there is no effective treatment in clinics because its pathogenesis is largely unknown. Although PF has been studied quite well from a biomechanical viewpoint, little has been done on PF biology. To better understand the cellular mechanisms of plantar fasciitis, in this study we aimed first to characterize biological properties of stem cells isolated from the sheath and the core of human PF tissues. Their biological responses to mechanical loading are also studied. Methods: Two stem cell populations isolated from the sheath (PF-S) and core (PF-C) parts of human PF tissues were investigated by characterizing their colony formation, stem cell marker expression, population doubling time (PDT), multi-differentiation potentials, and biological responses to mechanical loading. One-way ANOVA followed by Fisher’s PLSD for multiple comparisons was used for statistical analysis. A p-value < 0.05 was considered to be statistically significant. Results: PF-S grew quicker and formed larger colonies than PF-C cells (Fig. 1). More PF-S expressed nucleostemin (Fig. 2A), Oct- 4 (Fig. 2C), SSEA-4 (Fig. 2E) than PF-C cells (Fig. 2B, 2D, 2F). More PF-S were stained by collagen type IV (Fig. 3D), CD31 (Fig. 3A), and vimentin (Fig. 3B), and less stained by collagen I (Fig. 3C) than those of PF-C cells (Fig. 3E-I). More PF-S were differentiated into adipocytes (Fig. 4A), osteocytes (Fig. 4B), and chondrocytes (Fig. 4C) than PF-C cells (Fig. 4D-F). PF-S and PF-C respond to intensive mechanical stretching differentially in terms of gene expression levels of collagen I (Fig. 5A), IV (Fig. 5B), CD105 (Fig. 5C), non-tenocyte related genes (Fig. 5D-F), MMPs (Fig. 5G-H), and inflammation-related genes, COX-I and COX-II (Fig. 5I-J). Conclusion: This study characterized plantar fascia in detail at histological, cellular, and mechanobiological levels. Our results showed that plantar fascia consists of two distinct tissues sheath and core with differential structural and cellular properties. The cells isolated from sheath and core of human PF also differ in their response to mechanical loading. This information may be useful in determining the respective contributions of the sheath and core stem cells to the development of plantar fasciitis and in devising new biologic approaches for effective repair of injured PF in clinics.