Ryosuke Ikeguchi

Background: Longitudinal changes in skeletal muscle mass and quality after allogeneic hematopoietic stem cell transplantation remain unclear. This study used bioelectrical impedance analysis to assess these changes and their associations with physical function, infection, and acute graft-versus-host disease. Methods: This retrospective study included 111 adults who underwent allogeneic hematopoietic stem cell transplantation. Skeletal muscle mass index and phase angle, an indicator of muscle quality, were assessed by bioelectrical impedance analysis before transplantation, 4 weeks after transplantation, and at discharge. Patients were assigned to four combined categories based on normal or low muscle mass and quality. Outcomes included 6 min walk distance, infection, and acute graft-versus-host disease. Results: Skeletal muscle mass index and phase angle decreased significantly after transplantation ( p < 0.05), with phase angle declining earlier and more markedly. At discharge, 53.1% of patients were classified as Category 3. At 4 weeks, the decline in 6 min walk distance was significantly greater in Categories 2 and 3 than in Categories 0 and 1. In multivariable analyses, Categories 2 and 3 were independently associated with infection, whereas Category 3 was independently associated with acute graft-versus-host disease. Conclusion: Skeletal muscle mass and quality deteriorated after allogeneic hematopoietic stem cell transplantation, and low muscle quality was more closely associated with adverse outcomes. Pre-transplant bioelectrical impedance analysis-based assessment of muscle quality may help identify patients at risk of infection, acute graft-versus-host disease, and delayed physical recovery and may support further evaluation of prehabilitation strategies.

Purpose Sarcopenia is a common comorbidity in older adults. This study aimed to clarify the association between preoperative sarcopenia, based on the Asian Working Group 2025 (AWGS2025) criteria, and postoperative outcomes in older patients with early stage non-small cell lung cancer. Methods This retrospective study included patients aged ≥ 75 years who underwent lung resection for clinical stage I lung cancer. Sarcopenia was diagnosed based on grip strength and bioelectrical impedance-derived muscle mass measured according to the AWGS2025 criteria. The primary outcomes were postoperative pulmonary complications (PPCs), defined as Clavien–Dindo classification Grade ≥ 2 within 30 days, and unplanned readmission within 90 days after surgery. A logistic regression analysis was used to identify the factors associated with postoperative outcomes. Results Among the 107 patients, 28 (26%) were diagnosed with sarcopenia. The incidence of PPCs (32% [9/28] vs. 8% [6/79], P = 0.003) and unplanned readmission (18% [5/28] vs. 3% [2/79], P = 0.013) was higher in the sarcopenia group. Sarcopenia independently predicted PPCs (odds ratio [OR], 5.00; P = 0.020) and unplanned readmissions (OR, 9.17; P = 0.019). Conclusions Preoperative sarcopenia, diagnosed using the AWGS2025 criteria, is closely associated with PPCs and unplanned readmissions in older patients. Preoperative screening may facilitate risk stratification and improve perioperative care.

Peripheral nerve injuries (PNIs) often cause persistent sensory and motor deficits that impair quality of life. To improve outcomes, cell-based therapies have been explored, and Schwann cells (SCs) are considered a promising option because of their essential roles in myelination and neurotrophic support. However, the clinical use of autologous SCs is limited by donor site morbidity and challenges in large-scale expansion, leading to growing interest in human induced pluripotent stem cell (iPSC)–derived SCs. This study aimed to verify the therapeutic effects of iPSC-derived SCs in vivo and to determine whether the differentiation stage of the SCs influences their efficacy. We generated dibutyryl-cAMP–treated mature SCs and untreated immature SCs from iPSCs and transplanted them into a rat sciatic nerve crush injury model. Morphometric analysis showed that myelinated fiber density (fibers/mm ² ) was significantly higher in the mature SC group than in the control group (12 602 ± 1419 vs 10 105 ± 1673). Myelinated axon diameter (µm) was also significantly greater in the mature SC group (4.73 ± 0.25) compared with the immature SC (4.06 ± 0.28) and control (3.86 ± 0.15) groups. Electrophysiological testing demonstrated that compound muscle action potentials in the pedal adductor muscle were detected only in the mature SC group within 28 days after surgery. Western blot analysis of the tibialis anterior muscle showed significantly higher myosin heavy chain 1 (MYH1) expression in the mature SC group than in the control group. Quantitative reverse transcription-polymerase chain reaction revealed higher expression of bNGF , CCL2 , and LAMA2 in mature SCs than in immature SCs. Pathological analysis suggested accelerated Wallerian degeneration in the mature SC group. These results demonstrate that mature iPSC-derived Schwann cells, rather than immature ones, most effectively promote nerve regeneration both histologically and functionally in vivo, highlighting the critical importance of the SC differentiation stage for therapeutic efficacy.

Purpose Bioelectrical impedance analysis (BIA) has emerged as a simple, noninvasive method for evaluating skeletal muscle. However, BIA is sensitive to fluctuations in body water and can overestimate skeletal muscle mass, which may obscure true changes, particularly in the early post-transplant period, when body water content often increases. In this study, we explored whether correction formulas originally used in the dialysis field to estimate ideal dry weight could be applied to skeletal muscle measurements to reduce overestimation of skeletal muscle mass. Methods This retrospective observational study included patients who underwent allogeneic hematopoietic stem cell transplantation. Physical function and body composition were assessed before transplantation and 4 weeks after transplantation. Physical function was evaluated using knee extensor strength and the six-minute walk distance (6MWD). Body composition was assessed using appendicular skeletal muscle mass (ASM) as an index of muscle quantity, phase angle as an index of muscle quality, and the extracellular-to-total body water ratio (ECW/TBW) as an indicator of fluid balance. A correction formula for estimating ideal dry body weight was applied to adjust ASM. Differences between unadjusted and adjusted ASM were compared at each time point. Pre- and post-transplant changes in phase angle and ECW/TBW were also evaluated. Results Sixty-four adult patients aged 20–70 years (median age, 51.5 years) were included. After transplantation, adjusted ASM differed significantly from unadjusted ASM. Knee extensor strength, 6MWD, and phase angle (median, 4.4°to 3.9°, p < 0.001) decreased significantly, whereas ECW/TBW increased significantly (median, 0.391 to 0.399; p < 0.001). Unadjusted ASM did not change significantly from pre- to post-transplantation (median, 17.7 to 17.5 kg; p = 0.17), whereas adjusted ASM decreased significantly (median, 17.6 to 17.2 kg; p = 0.01). Conclusion Applying a dialysis-derived adjustment formula to skeletal muscle measurements may help correct overestimation of skeletal muscle mass due to increased body water content in the early post-transplant period. After transplantation, both adjusted ASM and phase angle decreased significantly. These results suggest that BIA may have potential utility during the immediate post-transplant period, although its clinical applicability requires further validation.

Purpose Late-onset non-infectious pulmonary complications (LONIPCs) represent significant sequelae of hematopoietic stem cell transplantation (HSCT), contributing to elevated non-relapse mortality rates. A comprehensive understanding of systemic conditions and prognostic indicators is essential for enhancing supportive care following onset. This study aims to compare respiratory and physical function between patients with LONIPCs and healthy controls, and to identify prognostic factors that influence survival outcomes in patients with LONIPCs. Methods This study included 41 LONIPCs patients admitted to Kyoto University Hospital for lung transplant evaluation. A healthy control group comprised matched living lung transplant donors. Comparisons included respiratory function tests, 6-min walk distance (6MWD), and erector spinae muscle cross-sectional area (ESMA). Multivariate Cox regression analysis was used to identify prognostic factors. Results LONIPCs patients demonstrated significantly reduced respiratory function and 6MWD compared to healthy controls. ESMA was also significantly lower in the patient group. Multivariate Cox regression revealed that decreased knee extensor strength and reduced ESMA were significant predictors of overall survival in patients with LONIPCs. Conclusion Impairments in respiratory and physical function are evident in LONIPCs patients. Modifiable factors such as lower limb muscle strength and skeletal muscle mass, particularly ESMA, are associated with prognosis and should be prioritized in rehabilitation strategies to improve patient outcomes.

Background: Recently, the immunomodulatory effects of mesenchymal stem cells have been reported in several studies. The purpose of this study was to evaluate the effect of the administration of human amnion–derived mesenchymal stem cells (hAm‐MSCs) in a rat vascularized composite allotransplantation model. Materials and Methods: A total of 18 Lewis (LEW) rats and 6 Brown‐Norway (BN) rats were used. Sixteen LEW rats as recipients were divided randomly into four groups: Isograft (Iso), Untreated (UT), FK, and MSC groups ( n = 4, each group). Hind limb transplantation was performed. In the Iso group, 2 LEW rats were used as donors. In the other groups, 6 BN rats were used as donors. In the UT group, no immunosuppressant was used. In the FK group, 0.2 mg/kg/day of FK506 (tacrolimus) was administered from day 0 to day 6. In the MSC group, 2 × 10 ⁶ hAm‐MSCs were administered on day 7 after tacrolimus administration (day 0–6). Graft survival was assessed by daily inspection, histology, and immunohistology with the TUNEL (terminal deoxynucleotidyl transferase dUTP nick‐end labeling) assay. Cytokine mRNA expression analysis using real‐time, reverse transcription PCR (RT‐PCR) of the grafts was analyzed. Results: Graft survival in the MSC group (14.8 days) was significantly prolonged compared with that of the FK group (13 days; p < 0.05). Histology and immunohistology with the TUNEL assay showed a significant reduction of mononuclear cell infiltration and apoptotic cells in the MSC group compared with the FK group ( p < 0.05). RT‐PCR analysis of cytokine mRNA expression showed a significant decrease of IL‐2 and an increase of TGFβ in graft muscle ( p < 0.05). Conclusions: hAm‐MSCs prolonged graft survival in the rat vascularized composite allotransplantation model. hAm‐MSCs could be an alternative immunomodulatory agent to avoid the side effects of conventional immunosuppressant.

Peripheral nerve injuries involving nerve defects remain challenging to treat. Although autologous nerve grafting is considered the gold standard, it has notable limitations, including donor site morbidity. To address this, we developed a scaffold-free Bio 3D conduit composed of human umbilical cord–derived mesenchymal stromal cells (UC-MSCs) using bioprinting technology. In this study, we evaluated its efficacy and safety in a canine ulnar nerve defect model. At 10 weeks postoperatively, the Bio 3D group showed better motor and sensory recovery compared with the allograft group, as demonstrated by the pinprick test, electrophysiological studies, and hypothenar muscle wet weight (0.978 ± 0.100 vs. 0.637 ± 0.151, n = 3). Morphometric analysis revealed greater axonal regeneration, including larger myelinated axon diameters (4.27 ± 0.342 µm vs. 3.69 ± 0.161 µm, n = 3) and thicker myelin sheaths (0.621 ± 0.088 µm vs. 0.497 ± 0.021 µm, n = 3). Immunostaining showed that the number of transplanted UC-MSCs diminished over time, likely after exerting their therapeutic effects. No adverse events, systemic abnormalities, or distant human cell migration was observed. These findings suggest that UC-MSC–derived Bio 3D conduits are a promising alternative for peripheral nerve regeneration, especially for patients wishing to avoid donor nerve harvesting.

Tumor surgery or trauma in the maxillofacial region may cause injuries to peripheral nerves, such as facial nerves. The gold standard of treatment for peripheral nerve injury has been autologous nerve grafting. Since new peripheral nerve regeneration technologies are required, three‐dimensional (3D) structures fabricated only from cells by using Bio 3D printers are attracting attention. Dental pulp stem cells (DPSCs) are a promising option as a cell source because of their high clonogenic, proliferative, and multidifferentiation potentials. In this study, nerve conduits were fabricated from DPSCs using a Bio 3D printer, and their potential for nerve regeneration was evaluated in a rat facial nerve injury model. DPSCs were obtained from wisdomteeth of patients and cultured. A 5 mm Bio 3D conduit was fabricated by using a Bio 3D printer. Six F344 rnu‐/rnu‐ rats with immune deficiency (10 weeks old, body weight: 190–240 g) were divided into two groups: a Bio 3D group ( n = 3) and a silicone tube group ( n = 3). The 5 mm Bio 3D conduits and silicone tubes were transplanted into 4 mm defects. Evaluation was performed at 12 weeks after the surgery. The whiskers of immunodeficient rats in both groups were moving. The number of myelinated axons was larger in the Bio 3D group than in the silicone group. Myelinated axon diameter (MAD) and myelin thickness (MT) of regenerated axons in the Bio 3D group were significantly greater than those in the silicone group (MAD: p < 0.01, MT: p < 0.05). In this study, we confirmed the nerve regeneration potential of Bio 3D structures fabricated from DPSCs that were transplanted into a rat model of facial nerve injury.

Surgery using skin flaps is essential for soft tissue reconstruction. However, postoperative ischemic injury of the skin flap is a major complication and a top concern after the surgery. Currently, evidence-based drugs to fully prevent ischemic injury are not available. The purpose of this study was to evaluate the effect of KUS121, a VCP modulator, on flap ischemia using a rodent model. 26 Sprague-Dawley rats were randomly divided into two groups. The experimental group was intraperitoneally administered with 100 mg/kg KUS121 dissolved in 5% glucose solution 1 hour before surgery and once per day after surgery. The control group received the same amount of glucose solution on the same schedule. On day 7, 33.6 ± 3.7% of skin flaps in the control group had developed black necrosis compared with 26.4 ± 3.6% in the KUS121 group (p < 0.01). Immunohistochemistry showed that the KUS121 treatment reduced the number of apoptotic cells in the distal third of the flap (p < 0.01); moreover, in the KUS121-treated rats, the number of cells expressing CHOP, an endoplasmic reticulum (ER) stress marker, in the middle third of the flap was significantly lower than in the controls (p < 0.01). We examined the mRNA expression of Ddit3 (CHOP) and Casp3 (caspase-3) on day one after the surgery; mRNA expression of both genes appeared to decrease in the KUS121 group, as compared with the control group, although differences between groups were not significant. Thus, in a random pattern flap, KUS121 reduces ER stress and the number of apoptotic cells, thereby reducing ischemic damage of the flap.