Revealing Molecular-Scale Structural Changes in Polymer Nanocomposites during Thermo-Oxidative Degradation Using Evolved Gas Analysis with High-Resolution Time-of-Flight Mass Spectrometry Combined with Principal Component Analysis and Kendrick Mass Defect Analysis.

This study introduces a novel method that utilizes evolved gas analysis with time-of-flight mass spectrometry (EGA-TOFMS) coupled with principal component analysis (PCA) and Kendrick mass defect (KMD) analysis, called EGA-PCA-KMD, to analyze complex structural changes in polymer materials during thermo-oxidative degradation. While EGA-TOFMS captures exact mass data related to the degradation components in the temperature-dependent mass spectra of the evolved products, numerous high-resolution mass spectra with large amounts of ion signals and varying intensities provide challenges for interpretation. To address this, we employed mathematical decomposition through PCA to selectively extract information about the ion series specific to the products that evolved from the degradation components. Additionally, KMD analysis was applied to the attribution of the exact mass signals extracted from the PCA, which categorizes and visualizes depending on the molecular compositions in a two-dimensional plot. The complex structural changes of the triblock copolymer thermoplastic elastomer and its nanocomposites containing nanodiamonds during thermo-oxidative degradation were elucidated using EGA-PCA-KMD to demonstrate the effectiveness of this characterization technique for polymer degradation. Furthermore, it is revealed that the formation of rigid matrix-filler interfacial interaction via the π-π stacking and chemical bonds in the nanocomposites contributes to improvement in the stability toward thermo-oxidative degradation. Our results highlight the benefits of EGA-PCA-KMD and provide valuable insights into polymer degradation.

Association between conditioning intensity and height growth after allogeneic hematopoietic stem cell transplantation in children.

BACKGROUND: The present study aimed to examine the association between the conditioning intensity and height growth in pediatric patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We reviewed the clinical records of 89 children with malignant diseases who underwent initial allo-HSCT between 2003 and 2021. Height measurements were standardized using standard height charts prepared by the Japanese Society for Pediatric Endocrinology to calculate standard deviation score (SDS). We defined short stature as a height SDS less than -2.0 in that reference. Myeloablative conditioning (MAC) comprised total-body irradiation at more than 8 Gy and busulfan administration at more than 8 mg/kg (more than 280 mg/m2 ). Other conditioning regimens were defined as reduced intensity conditioning (RIC). RESULTS: A total of 58 patients underwent allo-HSCT with MAC, and 31 patients received allo-HSCT with RIC. There were significant differences in the height SDS at 2 and 3 years after allo-HSCT between MAC and RIC group (-1.33 ± 1.20 vs. -0.76 ± 1.12, p = 0.047, -1.55 ± 1.28 vs. -0.75 ± 1.11, p = 0.022, respectively). Multivariate logistic regression analysis with the adjustments for potential confounding factors of patients less than 10 years of age at allo-HSCT and chronic graft-versus host disease demonstrated that MAC regimen was associated with a markedly increased risk of a short stature at 3 years after allo-HSCT (adjusted odds ratio, 5.61; 95% confidence interval, 1.07-29.4; p = 0.041). CONCLUSION: The intensity of conditioning regimen may be associated with short statures after allo-HSCT.

Epidural Spinal Cord Compression as the Presenting Manifestation of Acute Myeloid Leukemia: A Case Report and Literature Review.

We herein report a rare case of spinal cord compression due to epidural involvement of acute myeloid leukemia (AML). A 14-year-old boy presented with a 7-day history of back pain, paraplegia and hypoesthesia. Contrast-enhanced computed tomography revealed an epidural mass. Emergency laminectomy and resection of the mass were performed. Histopathologically, the resected mass was comparable to an extramedullary mass of AML. Chemotherapy was initiated, and complete remission was achieved. Neurological sequelae remained after the treatment. Based on the present and previous reports, spinal cord compression from epidural AML involvement may progress rapidly.

Association between muscle mass evaluated by computed tomography and the serum creatinine-cystatin C ratio in children with cancer: A cross-sectional study.

OBJECTIVE: There is limited knowledge about muscle-mass loss in childhood and adolescent patients with cancer. The aim of this study was to investigate the association between muscle mass evaluated by computed tomography (CT) and the serum creatinine-cystatin C ratio (CCR) in children and adolescents with cancer. METHODS: Patients age <18 y with cancer who underwent abdominal CT scans and blood sampling for serum creatinine and cystatin C within 1 wk before or after the CT scan between 2017 and 2019 at our hospital were retrospectively enrolled. A measurement was defined as a set of abdominal CT scans and serum creatinine and cystatin C levels. The psoas muscle cross-sectional area (PMCSA) was defined as the psoas major muscle area at the level of the fourth lumbar vertebra on axial CT. Statistical tests and modeling were performed as measurement-based analyses. RESULTS: A total of 109 patients and 204 measurements were included in the analysis. CCR showed a strong positive correlation with PMCSA (r = 0.75; P < 0.001). The association between CCR and PMCSA was observed in all age groups and both sexes. There was a clear trend of increased PMCSA across quartile categories of CCR (P < 0.001). On multivariate, generalized, estimating, equation, linear regression model analysis, examining factors associated with PMCSA, male sex, body surface area, and CCR were independent parameters for PMCSA. CONCLUSIONS: These results suggest that CCR may be a useful surrogate marker for muscle mass in cancer care for children and adolescents.

Can CD200R1 Agonists Slow the Progression of Osteoarthritis Secondary to Injury?

Post-traumatic knee osteoarthritis is characterized by cartilage degeneration, subchondral bone remodeling, osteophyte formation, and synovial changes. Therapeutic targeting of inflammatory activity in the knee immediately post injury may alter the course of osteoarthritis development. This study aimed to determine whether CD200R1 agonists, namely the protein therapeutic CD200Fc or the synthetic DNA aptamer CCS13, both known to act as anti-inflammatory agents, are able to delay the pathogenesis of injury-associated knee osteoarthritis in a murine model. Ten week old male C57BL/6 mice were randomized and surgical destabilization of the medial meniscus (DMM) to induce knee arthritis or sham surgery as a control were performed. CCS13 was evaluated as a therapeutic treatment along with CD200Fc and a phosphate-buffered saline vehicle control. Oligonucleotides were injected intra-articularly beginning one week after surgery, with a total of six injections administered prior to sacrifice at 12 weeks post-surgery. Histopathological assessment was used as the primary outcome measure to assess cartilage and synovial changes, while µCT imaging was used to compare the changes to the subchondral bone between untreated and treated arthritic groups. We did not find any attenuation of cartilage degeneration or synovitis in DMM mice with CD200Fc or CCS13 at 12 weeks post-surgery, nor stereological differences in the properties of subchondral bone. The use of CD200R1 agonists to blunt the inflammatory response in the knee are insufficient to prevent disease progression in the mouse DMM model of OA without anatomical restoration of the normal joint biomechanics.

The comparison of acute toxicities associated with craniospinal irradiation between photon beam therapy and proton beam therapy in children with brain tumors.

INTRODUCTION: This study aimed to evaluate acute toxicities associated with irradiation between the X-CSI (photon beam craniospinal irradiation) and P-CSI (proton beam craniospinal irradiation) groups in children with brain tumors. METHODS: Sixty-two consecutive patients who received initial craniospinal irradiation (CSI) for brain tumors in our center between January 1, 2011 and May 31, 2021, were included in the study. Acute toxicities were retrospectively evaluated during CSI using Common Terminology Criteria for Adverse Events version 5.0. Maximum grades of fatigue, headache, insomnia, nausea, vomiting, dermatitis, constipation, abdominal pain, oropharyngeal mucositis, and hematological toxicities were evaluated. RESULTS: Thirty-six patients received X-CSI, and 26 patients received P-CSI. The median dose of CSI was 18.0 Gy in the X-CSI group and 23.4 Gy (relative biological effectiveness) in the P-CSI group (p < 0.001). The P-CSI group had a lower incidence of more than grade 2 nausea (11.5% vs. 69.4%, p = 0.008) and vomiting (7.7% vs. 38.8%, p < 0.001), compared with the X-CSI group. Multivariate logistic regression analysis with adjustments for potential confounding factors of doses of CSI showed that proton radiation therapy was associated with a marked reduced risk of more than grade 2 nausea and vomiting during CSI (adjusted odds ratio, 0.050; 95% confidential interval, 0.011-0.24; p < 0.001). CONCLUSION: The present study suggests that P-CSI reduces the acute gastrointestinal toxicities associated with irradiation.

Poorly Differentiated Chordoma of the Clivus With Loss of SMARCB1 Expression in a Pediatric Patient: A Case Report.

Poorly differentiated chordoma (PDC) is a rare, aggressive subtype of chordoma. A two-year-old girl presented with cervical pain, limb paralysis and respiratory failure. Magnetic resonance imaging and positron emission tomography-computed tomography revealed a tumor compressing the pons at the clivus and osteoblastic metastatic lesions of the left upper arm and right iliac bone. Her tumors shrank substantially after treatment with chemotherapy and proton beam therapy. Our initial diagnosis was an atypical teratoma/rhabdoid tumor, but final diagnosis of PDC was made on the basis of the immunohistochemical expression of brachyury. In addition, the detection of SMARCB1/INI1 mutation confirmed the diagnosis of PDC.

Effect of Monoammonium Glycyrrhizinate on the Development of Hepatotoxicity After Initial Intrathecal Chemotherapy for Leukemia.

BACKGROUND/AIM: Chemotherapy for acute leukemia includes agents known to cause hepatotoxicity. This study evaluated the role of monoammonium glycyrrhizinate for the prevention of hepatotoxicity after the first methotrexate-containing intrathecal chemotherapy (ITC) in children and adolescents with leukemia. PATIENTS AND METHODS: Patients with newly diagnosed acute leukemia (age 0-18 years) who received ITC during the first week of induction therapy at our hospital between April 2016 and March 2021 were enrolled. Intravenous monoammonium glycyrrhizinate (IVMG) was defined as the intravenous administration of monoammonium glycyrrhizinate initiated on the day before or the day of the first ITC. RESULTS: Overall, 39 of 118 patients (33%) developed grade 3-4 hepatotoxicity. The inverse probability of treatment weighting logistic regression model showed that IVMG was not associated with the development of grade 3-4 hepatotoxicity (OR=1.9, 95%CI=0.808-4.468). CONCLUSION: IVMG did not protect against the development of grade 3-4 hepatotoxicity after the first methotrexate-containing ITC for leukemia.

Muscle mass change during chemotherapy in children with high-risk neuroblastoma: a retrospective case series of 24 patients.

The clinical characteristics, cause, and risk factors of sarcopenia are unclear in children. The aim of this study was to describe the course of and identify the factors related to muscle mass change during chemotherapy in children with neuroblastoma. A total of 24 consecutive patients aged below 18 years with newly diagnosed high-risk neuroblastoma between 2010 and 2018 in our hospital were enrolled in a case-series study. The psoas muscle index (PMI) was calculated as a parameter of muscle mass based on computer tomography (CT) images of the psoas muscle. PMIs were evaluated at 4 time points (TPs): TP1, at the diagnosis of neuroblastoma; TP2, after the first cycle of chemotherapy; TP3, after the third cycle of chemotherapy; and TP4, at the end of the induction chemotherapy. PMI recovery was defined as an increase in PMI between TP2 and TP4. The mean PMI decreased by 15% between TP1 and TP2 (TP1 7.09 ± 0.99 vs. TP2 6.01 ± 0.98, P < 0.001) and by 10% between TP1 and TP4 (TP1 7.09 vs. TP4 6.35, P = 0.004). PMI recovery between TP1 and TP2 was observed in 7 (29%) patients. The median age of patients with PMI recovery was significantly lower (2 vs. 4 years, P = 0.028), and the proportion of boys was significantly higher in patients with PMI recovery (100% vs. 41%, P = 0.017).Conclusion: This study demonstrated that prominent PMI reduction occurs during the early time of chemotherapy, and a younger age and male sex may be predictive factors for PMI recovery. What is Known: • Sarcopenia is a common disorder in elderly people. • Several causes and risk factors have been reported in adults. • Children with previous hematological malignancies have decreased physical activity. What is New: • Prominent muscle mass loss was observed early in children with high-risk neuroblastoma during chemotherapy. • Age and sex were found to be potentially associated with muscle mass recovery.

Low Multiplication Value of Absolute Monocyte Count and Absolute Lymphocyte Count at Diagnosis May Predict Poor Prognosis in Neuroblastoma.

Despite the growing evidences that immune dysfunction contributes to tumor progression, the prognostic value in patients with neuroblastoma regarding circulating immune blood cell counts has not been well characterized. To answer this, we conducted a retrospective study to evaluate the prognostic value of the circulating immune cell counts at diagnosis in a cohort of 55 patients with neuroblastoma. Based on a novel index by multiplying the absolute monocyte count (AMC)/µl and absolute lymphocyte count (ALC)/µl, we sub-grouped patients with AMC × ALC ≥ 1 × 106 (/µl)2 as high group and patients with AMC × ALC < 1 × 106 (/µl)2 as low group. In the entire cohort, the 4-year progression-free survival (PFS), and overall survival (OS) for high group (n = 38) vs low group (n = 17) was 81.7% (95%CI; 63.6-91.3%) and 90.7% (95%CI; 73.8-96.9%) vs 31.7% (11.6-54.1%) and 56.5% (29.7-76.4%; p < 0.001 for PFS and p = 0.015 for OS), respectively, suggesting that a low AMC × ALC is associated with poor prognosis. In the subgroup analysis for high-risk patients, the 4-year PFS and OS for high group (n = 17) vs low group (n = 13) was 59.8% (31.2-79.7%) and 79.8% (49.4-93.0%) vs 8.5% (0.5-31.7%) and 42.0% (15.4-66.8%; p < 0.001 for PFS and p = 0.089 for OS), respectively. Our data demonstrate that AMC × ALC at diagnosis is a cost-effective and easily measurable biomarker for predicting prognosis in neuroblastoma.

Pharmacokinetic analysis for model-supported therapeutic drug monitoring of busulfan in Japanese pediatric hematopoietic stem cell transplantation recipients.

This prospective observational study analyzed the pharmacokinetics of busulfan in Japanese children and evaluated the predicting accuracy of previous pediatric PPK models of busulfan. This study enrolled five patients (aged 2-12 years, BW 14-48 kg) receiving a busulfan-based conditioning regimen for hematopoietic stem cell transplantation at our hospital between January 2017 and December 2018. All patients received a 2-hour intravenous busulfan infusion four times daily for a total of 16 doses. After the infusions, 51 plasma samples were collected with the plasma busulfan concentration measured by liquid chromatography-tandem mass spectrometry. PPK model fitting was analyzed using the (%MPE) and the (%MAPE). Limited sampling strategies for estimating busulfan AUC were also evaluated. High interpatient variability was observed in the PK parameters. The most suitable PPK model that reflected our data was McCune's two-compartment model (%MPE -8.7, %MAPE 19.3). A combination sampling method using the busulfan concentration at 2 and 6 hours after the start of the first busulfan dose was found to be able to estimate AUC4 day . These results provide useful information on busulfan therapeutic drug monitoring in the Japanese pediatric population.

Simple Pretreatment for the Analysis of Additives and Polymers by Surface-Assisted Laser Desorption/Ionization Mass Spectrometry Using a Through-Hole Alumina Membrane as a Functional Substrate.

The analysis of additives and polymers was performed by desorption ionization using through-hole alumina membrane (DIUTHAME) as a functional substrate for both sample pretreatment and surface-assisted laser desorption/ionization (SALDI) mass spectrometry. Using the unique absorbing/filtering capabilities of DIUTHAME and investigating the solubility of analytes/bulk materials in some solvents, three pretreatment techniques were demonstrated with (1) the selective removal of hydrophilic poly(ethylene oxide) (PEO)-based components from a "PEO-monostearate" sample, (2) the on-chip filtration of solubilized decabromodiphenylether (DBDE) from a solution of polystyrene that had been preliminarily precipitated, and (3) the on-chip extraction of antioxidants (Irganox 1010, Irgafos 168, and dimyristyl 3,3'-thiodipropionate) from a suspension of polypropylene powder or from the powder itself. The extracted analytes were further mass-analyzed using a spiral high-resolution time-of-flight analyzer to assess their elemental composition or molecular distribution.

Effect of autotaxin inhibition in a surgically-induced mouse model of osteoarthritis.

Objective: Osteoarthritis (OA) is a degenerative joint disease with no approved disease modifying therapy. The enzyme autotaxin (ATX) converts lysophoshatidylcholine analogues to lysophosphatidic acid. Systemic inhibition of ATX reduces pain in animal models of OA; however, OA disease-modifying effects associated with ATX inhibition remain unknown. Here, we sought to determine whether local (knee joint) injection of an ATX inhibitor attenuates surgically-induced OA in mice. Methods: ATX expression was evaluated in human knee OA cartilage. Ten-week-old mice were subjected to surgically-induced OA. ATX inhibitor (PF-8380, 2.5ng/joint) was injected intra-articularly either at three and five weeks post-surgery or at two, four, six and eight weeks post-surgery and knee joints were evaluated by histopathology and immunohistochemistry to study the expression of catabolic and cell death markers. mRNA sequencing of human OA chondrocytes treated with/without ATX inhibitor was performed to identify differentially expressed transcripts, followed by pathway enrichment analysis. Results: ATX expression was elevated in severely degenerated cartilage compared to less degenerated human OA cartilage. In surgically-induced OA mice, intra-articular injection of ATX inhibitor at three and five weeks post-surgery partially protected knee joints from cartilage degeneration. Interestingly, earlier and more frequent ATX inhibitor injections did not confer significant protection. Immunohistochemical analysis showed decreased expression of catabolic and apoptotic markers with two ATX inhibitor injections. mRNA sequencing followed by pathway analysis identified pathways related to cholesterol analogue metabolism and cell-cycle that could be modulated by ATX inhibition in human OA chondrocytes. Conclusion: Local delivery of ATX inhibitor partially attenuates surgically-induced OA in mice.

Iron nanoparticle-labeled murine mesenchymal stromal cells in an osteoarthritic model persists and suggests anti-inflammatory mechanism of action.

Osteoarthritis (OA) is characterized by cartilage degradation and chronic joint inflammation. Mesenchymal stem cells (MSCs) have shown promising results in OA, but their mechanism of action is not fully understood. We hypothesize that MSCs polarize macrophages, which are strongly associated with joint inflammation to more homeostatic sub-types. We tracked ferumoxytol (Feraheme™, iron oxide nanoparticle)-labeled murine MSCs (Fe-MSCs) in murine OA joints, and quantified changes to joint inflammation and fibrosis. 10-week-old C57BL/6 male mice (n = 5/group) were induced to undergo osteoarthritis by destabilization of medical meniscus (DMM) or sham surgery. 3 weeks post-surgery, mice were injected intra-articularly with either fluorescent dye-(DiR) labeled or DiR-Fe-MSC or saline to yield 4 groups (n = 5 per group for each timepoint [1, 2 and 4weeks]). 4 weeks after injection, mice were imaged by MRI, and scored for i) OARSI (Osteoarthritis Research Society International) to determine cartilage damage; ii) immunohistochemical changes in iNOS, CD206, F4/80 and Prussian Blue/Sca-1 to detect pro-inflammatory, homeostatic and total macrophages and ferumoxytol -labeled MSCs respectively, and iii) Masson's Trichrome to detect changes in fibrosis. Ferumoxytol-labeled MSCs persisted at greater levels in DMM vs. SHAM-knee joints. We observed no difference in OARSI scores between MSC and vehicle groups. Sca-1 and Prussian Blue co-staining confirmed the ferumoxytol label resides in MSCs, although some ferumoxytol label was detected in proximity to MSCs in macrophages, likely due to phagocytosis of apoptotic MSCs, increasing functionality of these macrophages through MSC efferocytosis. MRI hypertintensity scores related to fluid edema decreased in MSC-treated vs. control animals. For the first time, we show that MSC-treated mice had increased ratios of %CD206+: %F4/80+ (homeostatic macrophages) (p<0.05), and decreased ratios of %iNOS+: %F4/80+ macrophages (p<0.01), supporting our hypothesis that MSCs may modulate synovial inflammation.

Pazopanib maintenance therapy after tandem high-dose chemotherapy for disseminated Ewing sarcoma.

The dismal prognosis of patients with disseminated Ewing sarcoma necessitates the development of novel treatment strategies. Pazopanib is an oral multi-targeted tyrosine kinase inhibitor that is active against advanced soft tissue sarcoma. However, the clinical activity and feasibility of pazopanib for treating Ewing sarcoma remain poorly understood. Moreover, clinical information on the use of tandem high-dose chemotherapy for Ewing sarcoma is limited. A 14-year-old boy with Ewing sarcoma was transferred to our hospital for treatment. Magnetic resonance imaging, computed tomography scans, and bone scintigraphy revealed multiple lesions in the pubis, ilium, ischium, femur, rib, cranial bone, thoracic vertebrae, sacrum, obturator muscle, adductor magnus muscle, testicular cord, and lungs. Bone scintigraphy after intensive chemotherapies confirmed that multiple abnormal accumulations were still present in the cranial bone and pubis. Subsequently, the patient received tandem high-dose chemotherapy including topotecan, and radiotherapy. Abnormal accumulations have disappeared in bone scintigraphy. Subsequently, pazopanib maintenance therapy was initiated. Despite the presence of innumerable lesions at diagnosis, the patient has been in near-complete remission for the past 1 year with pazopanib administration. This confirms that adding pazopanib maintenance therapy after tandem high-dose chemotherapy is a therapeutic option for cases with disseminated Ewing sarcoma.

Low-dose azacitidine maintenance therapy after allogeneic stem cell transplantation for high-risk pediatric acute myeloid leukemia.

The dismal prognosis of pediatric acute myeloid leukemia (AML) relapsing after hematopoietic stem cell transplantation (HSCT) requires exploration of novel strategies to prevent relapse. Azacitidine (AZA) maintenance therapy could potentially reduce the recurrence rate post HSCT. Here, we presents the cases of three children with high-risk AML post HSCT who were treated with low-dose AZA maintenance therapy, demonstrating the feasibility of this therapy. Currently, all three are in complete remission for 13-41 months despite their high-risk characteristics. Our encouraging data warrant larger prospective studies to assess the efficacy and safety of low-dose AZA maintenance therapy post HSCT for pediatric patients with high-risk AML.

Successful Combination Therapy of Liposomal Amphotericin B and Caspofungin for Disseminated Fusariosis in a Pediatric Patient With Acute Lymphoblastic Leukemia.

Disseminated fusariosis is a fatal infection in immunocompromised hosts. However, the optimal antifungal treatment for disseminated fusariosis has not yet been established. We report a case of disseminated fusariosis after chemotherapy for acute lymphoblastic leukemia, presenting with multiple skin, lung and kidney lesions and cerebrospinal fluid invasion. The combination therapy of liposomal amphotericin B and caspofungin resolved disseminated fusariosis successfully.

Clarithromycin co-administration does not increase irinotecan (CPT-11) toxicity in colorectal cancer patients.

PURPOSE: Irinotecan (CPT-11) is used to treat advanced colorectal cancer. The drug is activated by carboxylesterases and rendered inactive by CYP3A4. Recently, the efficacy of combining CPT-11 and anti-epidermal growth factor receptor (EGFR) agents was confirmed in patients with KRAS wild-type metastatic colorectal cancer. Clarithromycin (CAM) is a strong CYP3A inhibitor often used to prevent rash associated with anti-EGFR therapy. The objective of this study was to evaluate the risk of increased neutropenia and diarrhea in combining CPT-11 and CAM. METHODS: Retrospective analyses were conducted at Osaka National Hospital (Osaka, Japan) on the records of colorectal cancer patients treated with a CPT-11-containing regimen between November 2006 and January 2014. The incidence of neutropenia and diarrhea was compared between patients who received CPT-11 and CAM and patients who received CPT-11 without CAM. RESULTS: One-hundred and twenty-eight patients were included in this study, of whom 21 were concomitantly treated with CAM and 107 were not. There was no difference in the incidence of grade 3-4 neutropenia between the CAM co-administration group (10%) and the non-CAM group (16%) [Odds ratio: 0.56 (95% confidence interval: 0.12-2.62), p = 0.45]. No difference in the incidence of grade 3-4 diarrhea was found between the CAM co-administration group (0%) and the non-CAM group (4%) (p = 0.37). CONCLUSIONS: This study did not identify an increase in CPT-11 toxicity by co-administration with CAM.

Phase I/II Trial of Autologous Bone Marrow Stem Cell Transplantation with a Three-Dimensional Woven-Fabric Scaffold for Periodontitis.

Regenerative medicine is emerging as a promising option, but the potential of autologous stem cells has not been investigated well in clinical settings of periodontal treatment. In this clinical study, we evaluated the safety and efficacy of a new regenerative therapy based on the surgical implantation of autologous mesenchymal stem cells (MSCs) with a biodegradable three-dimensional (3D) woven-fabric composite scaffold and platelet-rich plasma (PRP). Ten patients with periodontitis, who required a surgical procedure for intrabony defects, were enrolled in phase I/II trial. Once MSCs were implanted in each periodontal intrabony defect, the patients were monitored during 36 months for a medical exam including laboratory tests of blood and urine samples, changes in clinical attachment level, pocket depth, and linear bone growth (LBG). All three parameters improved significantly during the entire follow-up period (p < 0.0001), leading to an average LBG of 4.7 mm after 36 months. Clinical mobility measured by Periotest showed a decreasing trend after the surgery. No clinical safety problems attributable to the investigational MSCs were identified. This clinical trial suggests that the stem cell therapy using MSCs-PRP/3D woven-fabric composite scaffold may constitute a novel safe and effective regenerative treatment option for periodontitis.