Platelet‐rich plasma protects rotator cuff‐derived cells from the deleterious effects of triamcinolone acetonide

Triamcinolone acetonide (TA) injections are widely used to treat enthesopathy, but they may induce adverse effects such as tendon impairment and rupture. Platelet‐rich plasma (PRP) is a blood fraction containing high platelet concentrations and various growth factors that play a role in tissue repair processes. The purpose of this study is to investigate whether TA has deleterious effects on human rotator cuff‐derived cells, and if PRP can protect these cells from the effects of TA. Human rotator cuff‐derived cells were cultured with and without TA and PRP, and the culture without any additive served as the control. Cell morphology was assessed at days 7 and 21. Cell viability was evaluated at days 1, 7, 14, and 21 by a water‐soluble tetrazolium salt assay. Induction of apoptosis was measured by immunofluorescence staining and flow cytometry at day 7. Induction of cleaved caspase‐3 was measured by immunofluorescence staining at day 7. The cells cultured with TA had a flattened and polygonal shape at day 7. The cells cultured with both TA and PRP were similar in appearance to control cells. Exposure to TA also significantly decreased cell viability, but cell viability did not decrease when PRP was added along with TA. The number of apoptotic cells increased with TA exposure, while addition of PRP prevented cell apoptosis. In conclusion, the deleterious effect of TA was prevented by PRP, which can be used as a protective agent for patients receiving local TA injections. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 976–982, 2013     

The quantitative and functional relation between insulin‐like growth factor‐I (IGF) and IGF‐binding proteins during human osteoarthritis

A previous hypothesis stated that during osteoarthritis (OA) increased insulin‐like growth factor (IGF) binding proteins (IGFBPs) sequester IGFs and limit their access to the cell. The objective of this article was to test this by: (1) quantifying IGF and IGFBP‐3 as well as their ratios in human OA cartilages, and (2) measuring the metabolic responses of diseased cartilage to IGF‐I and its IGFBP‐insensitive analogs. Knee or hip OA cartilages were staged for OA by histology. Cartilage slices were either extracted for assays of IGF proteins, or maintained intact as organ cultures. Proteoglycan (PG) metabolism ± IGFs was measured by use of the ³⁵S‐sulfate precursor. IGFBP‐3 (ng/mg protein) was weakly correlated with OA score by regression analysis (R² = 0.122; p = 0.040; n = 35). IGF‐I (ng/mg protein) was constant across all OA groups (ANOVA; p = .428, n = 18) and the IGF‐I/IGFBP‐3 ratios were > 1 in most samples. All OA cartilages responded to hrIGF‐I by increasing PG synthesis [average 2.29‐fold ± 0.55 (±SD) at saturation, n = 12] irrespective of OA score. The des (1–3) IGF‐I analog (which lacks the three N‐terminal amino acids) had similar maximal effects (average 2.23‐fold stimulation ± 0.71, n = 10), but it was more effective in two out of three samples at suboptimal doses. The effect of hrIGF‐I, des (1–3) IGF‐I, or the B‐chain analog on degradation was minimal. In summary, catabolism was insensitive to IGF‐I, and this was probably not due to IGFBPs. By contrast, IGF‐I exerted a robust stimulation of anabolism at sufficiently high doses, even though IGFBPs could tone down the ligand effect at low doses. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:465–474, 2008     

A critical role for donor‐derived IL‐22 in cutaneous chronic GVHD

Graft‐versus‐host disease (GVHD) is the major cause of nonrelapse morbidity and mortality after allogeneic stem cell transplantation (allo‐SCT). Prevention and treatment of GVHD remain inadequate and commonly lead to end‐organ dysfunction and opportunistic infection. The role of interleukin (IL)‐17 and IL‐22 in GVHD remains uncertain, due to an apparent lack of lineage fidelity and variable and contextually determined protective and pathogenic effects. We demonstrate that donor T cell–derived IL‐22 significantly exacerbates cutaneous chronic GVHD and that IL‐22 is produced by highly inflammatory donor CD4⁺ T cells posttransplantation. IL‐22 and IL‐17A derive from both independent and overlapping lineages, defined as T helper (Th)22 and IL‐22⁺ Th17 cells. Donor Th22 and IL‐22⁺ Th17 cells share a similar IL‐6–dependent developmental pathway, and while Th22 cells arise independently of the IL‐22⁺Th17 lineage, IL‐17 signaling to donor Th22 directly promotes their development in allo‐SCT. Importantly, while both IL‐22 and IL‐17 mediate skin GVHD, Th17‐induced chronic GVHD can be attenuated by IL‐22 inhibition in preclinical systems. In the clinic, high levels of both IL‐17A and IL‐22 expression are present in the skin of patients with GVHD after allo‐SCT. Together, these data demonstrate a key role for donor‐derived IL‐22 in patients with chronic skin GVHD and confirm parallel but symbiotic developmental pathways of Th22 and Th17 differentiation.     

Evaluation of Hyphecan (1‐4,2‐acetamide‐deoxy‐B‐D‐glucan polymer) on wound healing in a rodent model

Objective: To evaluate the effect of an artificial skin Hyphecan (1‐4,2‐acetamide‐deoxy‐B ‐D ‐glucan polymer) on wound healing in a rodent model. Materials and Method: The prospective study was conducted at a basic science laboratory at a tertiary teaching hospital. Two 4 cm × 4 cm full‐thickness wounds were created on the dorsal surface of 10 Spraque–Dawley rats and covered with Hyphecan and Kaltostat, respectively. Wounds were examined and measured on days 4, 10, 21 and 28, and would continue after day 28 until healed up completely. Punch biopsies (3 mm) were taken on days 4, 10 and 28 for histological examination of the response of healing and repair. Results: Despite the fact that the wound healing rate was similar for both groups on days 4, 10, 21 and 28, the average healing time for the Hyphecan group (29.1 ± 1.7 days) was significantly shorter statistically (P = 0.03) than the Kaltostat group (30.7 ± 2.8 days). Conversely, the marked healing response elicited by Hyphecan on day 4 persisted on days 10 and 28 in contrast to Kaltostat, which had only a mild degree of healing response on days 10 and 28. The study suggests that wounds treated by Hyphecan heal faster than Kaltostat. Conclusion: The findings provide basic scientific evidence supporting the clinical use of Hyphecan in different wounds and might also reduce the cost of wound management as Hyphecan is cheaper than Kaltostat and requires a shorter treatment time.      

A prospective observational study of immune reconstitution following transplantation with post‐transplant reduced‐dose cyclophosphamide from HLA‐haploidentical donors

Allogeneic hematopoietic cell transplantation (HCT) from HLA‐haploidentical donors with post‐transplantation high‐dose cyclophosphamide (PT/Cy‐haplo) now predominates worldwide. However, to our knowledge, no prospective study has compared immune reconstitution after PT/Cy‐haplo with that after conventional HCT. The mechanism by which chronic graft‐versus‐host disease (GVHD) is inhibited by PT/Cy‐haplo also remains unknown. We prospectively compared immune recovery patterns of lymphocyte subsets among four groups of adult patients with hematological disease who received HCT from either HLA‐matched related or HLA‐matched unrelated donors, cord blood transplantation, or reduced‐dose PT/Cy‐haplo. Counts of CD4+ T‐cell subsets, CD8+ T‐cell subsets, and NK cells on days 30 and 60 were often lower in PT/Cy‐haplo than those in HLA‐matched related HCT. The immune recovery pace in PT/Cy‐haplo subsequently caught up with that of the other grafts. The regulatory T cells (Tregs) to conventional CD4+ T‐cell (Tcon) ratio was significantly higher until day 90 in PT/Cy‐haplo. In multivariate analysis, a higher Tregs‐to‐Tcon ratio on day 60 was significantly associated with a lower incidence of chronic GVHD (P < 0.01). The preservation of Tregs by PT/Cy in the early phase might have resulted in a lower incidence of chronic GVHD.