Induction of iPSC-derived Prg4-positive cells with characteristics of superficial zone chondrocytes and fibroblast-like synovial cells.

BACKGROUND: Lubricin, a proteoglycan encoded by the PRG4 gene, is synthesised by superficial zone (SFZ) chondrocytes and synovial cells. It reduces friction between joints and allows smooth sliding of tendons. Although lubricin has been shown to be effective against osteoarthritis and synovitis in animals, its clinical application remains untested. In this study, we aimed to induce lubricin-expressing cells from pluripotent stem cells (iPSCs) and applied them locally via cell transplantation. METHODS: To generate iPSCs, OCT3/4, SOX2, KLF4, and L-MYC were transduced into fibroblasts derived from Prg4-mRFP1 transgenic mice. We established a protocol for the differentiation of iPSC-derived Prg4-mRFP1-positive cells and characterised their mRNA expression profile. Finally, we injected Prg4-mRFP1-positive cells into the paratenon, surrounding the Achilles tendons and knee joints of severe combined immunodeficient mice and assessed lubricin expression. RESULT: Wnt3a, activin A, TGF-ß1, and bFGF were applied to induce the differentiation of iPSC-derived Prg4-mRFP1-positive cells. Markers related to SFZ chondrocytes and fibroblast-like synovial cells (FLSs) were expressed during differentiation. RNA-sequencing indicated that iPSC-derived Prg4-mRFP1-positive cells manifested expression profiles typical of SFZ chondrocytes and FLSs. Transplanted iPSC-derived Prg4-mRFP1-positive cells survived around the Achilles tendons and in knee joints. CONCLUSIONS: The present study describes a protocol for the differentiation of iPSC-derived Prg4-positive cells with characteristics of SFZ chondrocytes and FLSs. Transplantation of lubricin-expressing cells offers promise as a therapy against arthritis and synovitis.

Induced pluripotent stem cell-derived tenocyte-like cells promote the regeneration of injured tendons in mice.

Tendons are dense fibrous structures that attach muscles to bones. Healing of tendon injuries is a clinical challenge owing to poor regenerative potential and scarring. Here, we created reporter mice that express EGFP, driven by the promoter of the tendon-specific Scleraxis (Scx) transcription-factor gene; we then generated induced pluripotent stem cells (iPSCs) from these mice. Utilising these fluorescently labelled iPSCs, we developed a tenogenic differentiation protocol. The iPSC-derived EGFP-positive cells exhibited elevated expression of tendon-specific genes, including Scx, Mohawk, Tenomodulin, and Fibromodulin, indicating that they have tenocyte-like properties. Finally, we demonstrated that these cells promoted tendon regeneration in mice after transplantation into injured tendons reducing scar formation via paracrine effect. Our data demonstrate that the tenogenic differentiation protocol successfully provided functional cells from iPSCs. We propose that pluripotent stem cell-based therapy using this protocol will provide an effective therapeutic approach for tendon injuries.

"Proceedings of the 22nd Aschauer Soiree on Growth and Health Screening", held at Altenhof, Germany, November 15th, 2014.

Twenty-five scientists met at Aschauhof, Altenhof, Germany, to discuss various aspects of the complex network of modern health screening, focusing on current scientific topics including medical sciences, human biology, and mathematics; on problems in implementing these results at the practical level of physicians, nurses, technicians, and engineers; and the level of administrative and political decisions. Whereas major scientific advancements have been published in the understanding and the bio-statistical evaluation of anthropometric screening parameters such as serial measurements of height and weight for preventive medical check-ups, BMI screening and surveillance in schools, etc., the implementation of these advancements into current health screening concepts, strategies and decision-making is poor. Fear of discrimination, misperception of body image, behavioural responses and political concerns, meanwhile dominate and negatively interfere with the implementation of recent scientific results into public health screening concepts and practices.

Incidence and characteristics of carpal fractures occurring concurrently with distal radius fractures.

PURPOSE: To investigate the incidence and characteristics of carpal fractures occurring concurrently with distal radius fractures and to determine the risk factors for this combination. METHODS: We retrospectively analyzed 161 consecutive patients with 170 distal radius fractures who were treated between 2007 and 2011. Posteroanterior, lateral, and oblique radiographs of the wrist were examined, as were computed tomography scans when available. We evaluated the incidence and characteristics of carpal fractures occurring concurrently with distal radius fractures and the patient factors of gender, age, AO/ASIF classification, and energy of the injury. RESULTS: Of the 170 distal radius fractures, 11 (7%) also had 1 or 2 carpal fractures. Of the 15 carpal fractures, 8 were scaphoid, 2 triquetrum, 2 pisiform, 1 capitate, 1 trapezium, and 1 hamate. Eleven of the 15 carpal fractures were diagnosed by computed tomography alone. Male gender, patients of lower mean age, AO/ASIF type B, and high-energy trauma significantly raised the risk of simultaneous fractures of the distal radius and carpals. CONCLUSIONS: The incidence of carpal fractures occurring concurrently with distal radius fractures was not negligible, and almost all carpal fractures had no or minimal displacement. Suspicion of carpal fractures occurring concurrently with distal radius fracture should be high, and computed tomography should be considered, in males, young patients, and those with AO/ASIF type B fractures and high energy trauma.