Identification of the tendon/ligament stem cell in mice and humans

Lingling Hu and colleagues identified a tendon and ligament stem cell population in mice and humans. The cells were defined as Lin-Thy1.2-Sca-1-CD73+CD140α- and showed self-renewal and the ability to generate tenocyte-lineage cells. In vivo lineage tracing based on somatic variants placed these cells at the top of the tendon and ligament differentiation hierarchy. In a mouse model of lumbar spinal stenosis, induction of ligamentum-flavum hypertrophy changed the cells’ differentiation program. The authors describe this as calcium-signaling-dependent, cell-intrinsic reprogramming that increases tenocyte output. The work offers a cellular mechanism for a common degenerative spinal condition and points to calcium signaling as a possible future drug target. It is not a stem-cell replacement therapy and does not show that injecting cells repairs ligaments or extends healthspan. The human component identifies and characterizes cells; the disease mechanism and intervention evidence are mainly preclinical. The paper also includes disclosed commercial relationships among some authors, including stock, board, consulting, or research-support interests. Clinical translation would require human validation, target-specific drug development, and safety testing. It should not be used to justify unapproved stem-cell injections for back pain.

Overall, this work identifies the TLSC and establishes dysregulated differentiation of this cell as a mechanism contributing to LSS.