Biology subjects

Bastani, M.

Publications and source records attributed to Bastani, M..

3 recordsLinked to original sources

bioRxiv2026

Tendon-derived injectable bio-instructive gel augments tenogenic differentiation of iMSC-SCX cells and extracellular matrix remodeling

In the US, 33 million musculoskeletal injuries have been reported per year, with 50% involving tendons and ligaments in both athletic and aging populations. Tendon repair often results in the formation of biomechanically inferior scar tissue rather than functional regeneration. Local cell therapy is garnering significant interest in tendon repair because it provides a targeted means to repopulate defects with potent therapeutic cells. Here, we developed a porcine tendon-derived thermoresponsive extracellular matrix hydrogel (TG) as an injectable, bio-instructive carrier for scleraxis-overexpressing induced mesenchymal stem cell derived tenocytes (iTenocytes), with the goal of improving cell retention and overall transplantation success. TG was compositionally distinct from purified collagen (PC, from rat tail type 1 collagen) and exhibited favorable material properties for a minimally invasive percutaneous strategy, including thermoresponsive gelation, shear-thinning injectability, retention at the injection site, and controlled biodegradation. In vitro, TG supported three-dimensional cell residence, promoted cell interconnectivity and redistribution at the matrix interface, and increased collagen type I release from iTenocytes compared to those embedded in PC. Transcriptomic and proteomic analyses further showed that TG enhanced programs associated with tenogenic maturation, extracellular matrix assembly, focal adhesion, mechano-transduction, and remodeling. In a rat Achilles tendon partial defect model, both optical imaging and histological analyses demonstrated retention of iTenocytes at the injection site. Additionally, confocal imaging demonstrated retention of iTenocytes within the defect site for up to 10 days. Together, these findings identify TG as a biofunctional injectable carrier that supports the tenogenic characteristics of iTenocytes and enhances their local persistence after transplantation.

cell biology↗

bioRxiv2026

Age-Dependent Fibroblast Programs Govern Regenerative and Fibrotic Tendon Repair

Tendon injuries often result in fibrosis, compromising function and predisposing to re-injury. Here, we used a full-width, non-repair Achilles tendon transection model in young (3 weeks old) and adult (18-20 weeks) rats to elucidate the cellular mechanisms governing regenerative versus fibrotic healing. Functional and biomechanical analyses revealed that young tendons recovered motion and load-bearing capacity more rapidly but exhibited more fibrotic early healing. Single-nuclei RNA sequencing identified seven major cell populations within the connective tissue compartment. Adult tendons maintained a "synthetic fibroblast" population marked by upregulated ECM synthesis, reduced stress-related gene expression, whereas young tendons favored expansion of Cxcl12/Lrp6/Gas6 fibrotic fibroblasts linked to oxidative and pro-angiogenic signaling. The young group showed sustained activation of Nox4-Gas6 pathways driving a self-reinforcing fibrotic circuit. These findings define a fibroblast lineage bifurcation that dictates oxidative stress signaling as a key regulator of fibrotic remodeling, highlighting potential therapeutic targets to promote regenerative tendon repair.

developmental biology↗

bioRxiv2026

Modulating Inflammation in Post-Traumatic Osteoarthritis using iPSC-derived Anti-inflammatory Macrophages

Post-traumatic osteoarthritis (PTOA) is a common long-term consequence of joint injury and a major cause of chronic pain and disability, yet no disease-modifying therapies are currently available. A central barrier to effective intervention is the persistence of maladaptive synovial inflammation, driven in part by macrophage-mediated signaling that sustains tissue degeneration and pain. Here, we developed a scalable, chemically defined platform to generate human induced pluripotent stem cell (iPSC)-derived anti-inflammatory macrophages (iMac-M2) as an off-the-shelf cell therapy designed to restore joint immune homeostasis after injury. These cells maintained a stable anti-inflammatory phenotype and function under osteoarthritis-relevant inflammatory conditions and suppressed inflammatory and catabolic responses in human joint cell co-culture systems. In a preclinical model of PTOA, intra-articular delivery of iMac-M2 after injury improved functional and structural outcomes while modulating synovial inflammatory and pain-associated transcriptional programs. Treatment was well tolerated, with no evidence of systemic immune activation or ectopic tissue formation. Together, these findings support iPSC-derived macrophage therapy as a clinically translatable immunomodulatory strategy to interrupt early inflammatory drivers of PTOA and preserve joint health following injury.

cell biology↗