Autologous Stem Research Articles

Orphan designation: Autologous human bone marrow-derived haematopoietic and mesenchymal stem cells depleted of erythrocytes, monocytes and lymphocytes, Treatment of spinal cord injury

Orphan designation: Autologous human bone marrow-derived haematopoietic and mesenchymal stem cells depleted of erythrocytes, monocytes and lymphocytes, Treatment of spinal cord injury

Treatment of Early Knee Osteoarthritis With Autologous Adipose-derived Mesenchymal Stem Cells

Treatment of Early Knee Osteoarthritis With Autologous Adipose-derived Mesenchymal Stem Cells

Autologous Hematopoietic Stem Cells Are a Preferred Source to Generate Dendritic Cells for Immunotherapy in Multiple Myeloma Patients.

In multiple myeloma (MM), dendritic cells (DCs), and their precursors are prone to malignant cell-mediated regulation of function leading to low efficacy of DC vaccine. DCs taken directly from MM patient's body or derived from monocytes are fewer in numbers and are also dysfunctional. Here, we investigated the functionality of Hematopoietic stem cell-derived DCs (SC-DCs) from MM patients. Mature-MM-SC-DCs showed all essential functions like antigen uptake, allogenic T cells simulation and migration comparable to those derived from healthy donor (HD) samples. A comparison of Mo-DCs and SC-DCs obtained from the same MM patients' samples revealed that the expression of IL-6 was higher in the precursors of Mo-DCs leading to their impaired migration. In addition, expression of CCR7 which is responsible for DCs migration was found to be lower in MM-Mo-DCs. The chromatin permissiveness as observed by H3K4me3 histone modification at the Ccr7 promoter in MM-Mo-DCs was significantly lower than those in MM-SC-DCs. Levels of Zbtb46- a hall mark DC transcription factor mRNA was also found to be reduced in MM-Mo-DCs. Cytotoxic T cells generated from MM-SC-DCs from autologous naïve T cells exhibited reduced antitumor activity because the T cells were exhausted. Blocking of CTLA-4 on autologous T cells could partially restore T cell proliferation and activation. Thus, a combination of MM-SC-DC vaccine and anti-CTLA-4 antibody may serve as a better candidate for immunotherapy of MM. This study has implications in increasing the efficacy of cancer immunotherapy in MM.

Sintilimab for relapsed/refractory classical Hodgkin’s lymphoma: Extended follow-up on the multicenter, single-arm phase II ORIENT-1 study.

7533 Background: Classical Hodgkin’s lymphoma (cHL) is characterized by chromosome 9p24.1 alterations and PD-1 ligand overexpression. Sintilimab, a programmed death-1 checkpoint inhibitor, has demonstrated efficacy in relapsed/refractory cHL after the primary analysis of the ORIENT-1 study. Here, we report the updated safety and efficacy prolines after extended follow-up. Methods: ORIENT-1 is a multicenter, single-arm, phase II study in China. Classical Hodgkin’s lymphoma patients who had failed ≥2 lines of systemic therapy, including autologous hematopoietic stem cell transplantation (HSCT) were enrolled. Sintilimab, 200 mg IV was given every 3 weeks, until disease progression, death, unacceptable toxicity, or withdrawal from study. The primary endpoint was objective response rate (ORR) assessed by an independent radiological review committee (IRRC) according to 2007 IWG criteria. Results: 96 patients were treated. As of the data cutoff on 16 October, 2018 72.9% of patients were continuing treatment with a median follow-up of 14 months. Median number of treatment cycles was 20 (range: 1 to 26). ORR was 85.4% (82/96, 95%CI: 76.7 to 91.8) based on IRRC review. Twenty-eight patients (29.2%) achieved complete response (CR) by PET scan. At the time of analysis, 59 out of 82 patients who had achieved complete or partial response continued to have an on-going response. The median duration of response (DoR) and progression free survival (PFS) have not been reached. The most common treatment-related adverse event (TRAE) was pyrexia (40.6%, 39/96), 92.3% of which was grade 1 or 2. The most common grade 3 or 4 TRAEs were pyrexia (3.1%) and anemia (3.1%). One death occurred which was not considered treatment related. Conclusions: ORIENT-1 study has the largest cohort of cHL patients in China treated with a PD-1. In addition to a high rate of response, sintilimab also demonstrated durable efficacy and favorable long-term safety profile after extended follow-up. Clinical trial information: NCT03114683.

Treatment of advanced gastrointestinal cancer with genetically modified autologous mesenchymal stem cells: Final results of the phase 1/2 TREAT-ME-1 trial.

e14648 Background: TREAT-ME-1, a Phase 1/2 open-label, first-in-human, first-in-class trial, evaluated the safety, tolerability and efficacy of treatment with genetically modified autologous mesenchymal stromal cells (MSC),MSC_ apceth_101, in combination with ganciclovir in patients with advanced gastrointestinal adenocarcinoma. Methods: All patients (6 in Phase 1; 7 in Phase 2) received three treatment cycles of MSC_apceth_101 on Day 0, 7, and 14 followed by ganciclovir administration according to the manufacturer’s instructions for 48─72 hours after MSC_apceth_101 injection. Three patients were treated with a total dose of 1.5 x 106cells/kg MSC_apceth_101 (DL1). Ten patients were treated with a total dose of 3.0 x 106cells/kg MSC_apceth_101 (DL2). Immunological and inflammatory markers were assessed.Time to progression, overall survival was evaluated by RECISTwithin 56 days after administration of MSC_apceth_101 administration. Results: A total of 54 AEs occurred in 9/13 patients, thereof 18 AEs in three patients of DL1 and 36 AEs in six patients of DL2. Six AEs were CTC-AE grade 3, all other AEs were lower CTC-AE grades.Five SAEs emerged in two patients of DL1 and six SAEs in four patients of DL2. Eight patients achieved stable disease (change in target lesions of -2 to +28%). For all patients, the median time to progression was 1.9 months (95% CI: 1.3, 3.6 months). Median overall survival could not be estimated as 8/10 patients were still alive at the end of the study (one year) and therefore censored. Post-study observation of patients showed a median overall survival of 15.6 months (ranging from 2.2─27.0 months). Treatment with MSC_apceth_101 and ganciclovir did not induce a consistent increase or decrease in levels of any of the tumor markers analyzed. No clear trends in the immunological markers assessed were observed. Conclusions: MSC_apceth_101 in combination with ganciclovir was safe and tolerable in patients with advanced gastrointestinal adenocarcinoma, with preliminary signs of efficacy in terms of clinical stabilization of disease. Clinical trial information: NCT02008539.

Durability of complete response after blinatumomab therapy for refractory/relapsed aggressive B-cell non-Hodgkin lymphoma.

e19041 Background: Achieving durable response in patients (pts) with relapsed/refractory (R/R) aggressive B-cell lymphoma (B-NHL) is challenging. Blinatumomab, a bispecific T-cell engager (BiTE) immunotherapy targeting CD19-expressing cancer cells, has shown promising efficacy in pts with R/R aggressive B-NHL. We report the durability of complete response (DOCR) in pts treated with blinatumomab. Methods: The DOCR in pts with R/R aggressive B-NHL responding to blinatumomab was assessed using data from two phase 2 studies (study 1 [N = 25], NCT01741792; study 2 [N = 41], NCT02910063) in pts with R/R aggressive B-NHL. CR was assessed using Cheson (study 1) and Lugano (study 2) criteria. Time-to-event variables were analyzed using the Kaplan-Meier (KM) method. Results: Baseline pt characteristics in the pooled analysis were: median age 59 years (range, 41–77); 54% men; 54% treatment refractory; median 2 lines of prior therapy (range, 1–7); and 15% with prior autologous hematopoietic stem cell transplant. Of 25 pts treated with blinatumomab in study 1, 4 (16%) evaluable pts achieved CR. Of 41 pts treated with blinatumomab in study 2, 9 (22%) achieved CR. Median DOCR was not reached (Table). At a median follow-up of 9.1 months in the pooled analysis, 3 pts (23%) had relapsed (study 1, n = 2 [50%]; study 2, n = 1 [11%]). At 12 and 18 months, the KM probability of maintaining CR in the pooled analysis was 53.0% (95% confidence interval [CI], 8.5, 85.0). Conclusions: For pts with R/R aggressive B-NHL who received blinatumomab, a durable response is possible. Longer-term follow up is needed to fully characterize the DOCR to blinatumomab. Clinical trial information: NCT01741792; NCT02910063. [Table: see text]

Outcomes of tbo-filgrastim, filgrastim-sndz or filgrastim for mobilization in patients undergoing an autologous hematopoietic stem cell transplant: A single center experience.

e19000 Background: Studies have reported that use of filgrastim (G) or any biosimilar result in similar stem cell yield during hematopoietic stem cell mobilization, but little is known on the effect of these biosimilars on length of hospitalization for the transplant procedure, engraftment, and long term survival of autologous hematopoietic stem cell transplant (HSCT) patients. Beginning January 2017, the Henry Ford Cancer Institute (HFCI) began utilizing tbo-filgrastim (TBO) and filgrastim-sndz (SNDZ) as part of mobilization. This study was conducted to evaluate transplant specific outcomes in HSCT patients comparing biosimilar and reference filgrastim products. Methods: This study retrospectively evaluated all patients treated at HFCI who received G-CSF based mobilization for HSCT between 1/2017 and 11/2018. Patient-, mobilization- and transplant specific variables were collected and analyzed. Results: A total of 113 patients underwent stem cell mobilization followed by collection and autologous HSCT. Of the 73 patients analyzed, 62% had a diagnosis of Multiple Myeloma (MM), 22% had Non-Hodgkin Lymphoma (NHL). Approximately 45% of patients received TBO, 44% received G and remainder received SNDZ. The percentage of patients who proceeded to HSCT was 86%. There was no difference in adequate CD34+ yield among the three G-CSF products (P = 0.074). There was no difference in mobilization associated complications including bone pain and thrombocytopenia. Plerixafor use was similar among the groups (P = 0.55). Actual CD34+ (P = 0.31) and the number of apheresis sessions required to collect an adequate CD34+ yield (P = 0.30) were not different among the groups. No significant differences were noted in time to neutrophil (P = 0.96) or platelet engraftment (P = 0.91) and hospital length of stay (P = 0.78). We found similar rates of infection, febrile neutropenia, and mucositis among the three groups. Relapse rates were also similar among the groups. Conclusions: In our institution transplant related outcomes were similar among patients who received TBO, SNDZ, and G as part of their pre-transplant mobilization protocol.

Effectiveness of Autologous Adipose-derived Stem Cells in the Treatment of Knee Cartilage Injury

Effectiveness of Autologous Adipose-derived Stem Cells in the Treatment of Knee Cartilage Injury

ELARA: A phase II, single-arm, multicenter, open-label trial investigating the efficacy and safety of tisagenlecleucel in adult patients with refractory/relapsed follicular lymphoma (r/r FL).

TPS7573 Background: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor-T cell (CAR-T) therapy that was approved for the treatment of pediatric and young adult patients up to 25 years of age with r/r B-cell acute lymphoblastic leukemia in 2017 (Maude et al. NEJM. 2018), as well as for the treatment of adult patients with r/r diffuse large B-cell lymphoma in 2018 (Schuster et al. NEJM. 2018). FL is the second most common non-Hodgkin lymphoma in the Western hemisphere, with limited treatment options in patients refractory to or relapsing after standard therapies. In a phase 2a study of patients with r/r CD19+ lymphomas, 10 of 14 (71%) patients with r/r FL treated with tisagenlecleucel achieved a durable complete remission at a median follow-up of 28.6 months (Schuster et al. NEJM. 2017). Here we introduce ELARA, a phase 2 study evaluating the efficacy and safety of tisagenlecleucel in patients with r/r FL. Methods: ELARA is a phase 2, single-arm, multicenter, open label trial. Eligible patients must be ≥18 years of age, have radiographically measurable grade 1, 2, or 3A r/r FL that is refractory to a second or later line of systemic therapy (including an anti-CD20 antibody and an alkylator), or relapsed within 6 months after completion of a second or later line of systemic therapy, or relapsed during anti-CD20 antibody maintenance (following ≥2 lines of therapy as above) or within 6 months after maintenance completion, or relapsed after autologous hematopoietic stem cell transplant (HSCT). Patients with central nervous system involvement, or those who received prior anti-CD19 therapy, gene therapy, adoptive T-cell therapy, or allogeneic HSCT are not eligible. The primary endpoint of this study is complete response rate based on Lugano classification response criteria. Secondary outcomes include overall response rate, duration of response, overall survival, cellular kinetics, immunogenicity, safety, and patient-reported outcomes. Estimated enrollment for this study is 113 patients. The study is currently open to patient enrollment. Clinical trial information: NCT03568461.

Utilization and outcomes of high-dose chemotherapy and stem-cell rescue in patient with testicular cancer from 2005 to 2014 in United States.

e18246 Background: Testicular tumors are potentially curable by means of high-dose chemotherapy plus hematopoietic stem-cell rescue. This regimen is commonly used as salvage therapy, third-line or later therapy in patients with platinum-refractory disease. The utilization and real-world outcomes and complications of patients with testicular cancer undergoing autologous hematopoietic stem cell transplant (aHSCT) in United States are unknown. Methods: We queried National Inpatient Sample, a large inpatient data set in the United States, from 2005 to 2014 for male patients with testicular cancer or multiple myeloma (control group) receiving aHSCT and compared outcomes between these groups. The primary outcome was in-hospital mortality rate, and the secondary outcomes included in-hospital complications of aHSCT, length of stay and total charges. Outcomes were assessed by means of univariate analysis, multivariate regression and propensity score matched-pair analysis. Results: A total of 391 patients (weighted N = 1,909) with testicular cancer and 4,809 male patients (weighted N = 23,501) with multiple myeloma who underwent aHSCT from 2005 to 2014 were identified. Mean age of patients with testicular cancer was 32.3 years vs 59 years for multiple myeloma patients (p < 0.001) There were no differences in in-hospital mortality rates (1.5% vs 1.4%, p = 0.85) or rates of intubation (2.3% vs 1.6%, p = 0.36), sepsis (7.7% vs 7.5%, p = 0.94), bacteremia (13.5% vs 15.6%, p = 0.42), or stomatitis (43.8% vs 38.8%, p = 0.87) between patients with testicular cancer and multiple myeloma receiving autologous HSCT. However, utilization of total parenteral nutrition was higher in patients with testicular cancer (12.9% vs 4.7%, p < 0.001). There was no difference in length of stay (17.5 vs 17.5 days, p = 0.77) and total charges (121,120$ vs 123,729$, p = 0.74) between two groups. The results were consistent in multivariate and propensity score matched-pair analysis. Conclusions: The in-hospital outcomes of patients with testicular cancer receiving aHSCT appears to be similar to patients with multiple myeloma. However, overall utilization of aHSCT for testicular cancer appears to be low in United States.

Intracavernous application of autologous bone marrow stem cells for erectile dysfunction unresponsive to medical treatment: a clinical case

Background & Aim Stem cell therapy for erectile dysfunction is a field that has aroused the interest of the scientific society. Numerous preclinical studies have demonstrated the efficacy and safety of this therapeutic modality. However, the clinical experience of stem cells in erectile dysfunction remains very limited. We present a case of severe erectile dysfunction resistant to iPDE5, related to long-term diabetes mellitus treated with intracavernous stem cells. Methods, Results & Conclusion The intervention was intracavernous autologous bone marrow stem cell transplantation, in a single application. A 50-week follow-up was performed, evaluating the therapeutic response by means of several standardized clinical questionnaires, penile doppler ultrasound and the presence of adverse effects. Among the results obtained, we registered a maximum clinical response at week 12 of follow-up, which subsequently decreased progressively. Ultrasonographic findings revealed the presence of neovascularization emerging from the cavernous arteries at the end of follow-up. Although there is still insufficient evidence and standardization of therapeutic protocols, this result encourages future research of SCs as a possible therapeutic modality. Randomized clinical trials should be done in order to respond doubts regarding this procedure.

Natural conditioning of mesenchymal stem cells from multiple sclerosis patients enhances their immune-modulating potential

Background & Aim Background Multiple sclerosis (MS) is the most frequent chronic inflammatory, demyelinating and neurodegenerative disease of the Central Nervous System (CNS) in young adults. The use of Autologous Mesenchymal stem cells (MSCs) have been investigated to treat MS for the past decades .Outcomes of non-standardized clinical trials have been inconsistent and calls for the use of allogenic MSCs have recently increased due to suggestions that the disease is affecting the therapeutic aspects of MSCs. Aim This work aims to investigate the influence of the genetic makeup of MS patients, the environmental factors involved in the etiology of MS or the immunomodulatory drugs taken by patients on their Bone Marrow derived Mesenchymal Stem Cells (MS-MSCs) compared to healthy donors, Control MSCs (CTR-MSCs). MSCs characteristics and immune- modulatory therapeutic potential was analyzed. Methods, Results & Conclusion Methods MSCs from 8 MS patients and 3 controls were characterized using microscopy, flow cytometry of surface markers, tri-lineage inherent and induced differentiation potential. For a comprehensive analysis on the transcriptome level, Affymetrix HTA microarray chips were used. In addition, Multiplex Enzyme Linked Immunosorbent Assay (ELISA) immunoassay to assess the Cytokine and chemokine secretion by MSCs was performed using the 27-plex human inflammatory kit (Biorad). Furthermore, coculture experiments of MS-MSCs from with T cells and DCs were conducted. Results MS-MSCs passed all the MScs characterization criteria. Microarray Analysis reveals the differential expression of two disease associated markers in MS-MSCs; miRNA-599 and the signal transducing gene T-cell activation RhoGTPase activating protein TAGAP. On the other hand, MS-MSCs showed an upregulation of important immunoregulatory genes in MS-MSCs such as TGFb1, the potent Treg differentiation factor. Moreover, IL-10 and other anti-inflammatory cytokines’ levels were higher in co-cultures of T cells with MS-MSCs. While, mDCs decreased in co-cultures with MS-MSCs. Conclusion The MS disease-related or medication-related cellular and biochemical changes in the bone marrow microenvironment does not appear to have a negative impact on the immune- modulation potential of BM-MSCs. On the contrary, there seem to have a positive conditioning effect of the inflammatory milieu which enhances the modulation of both the innate and the adaptive immunity.

Tu1249 – Autologous Haematopoetic Stem Cell Transplant (HSCT) May Improve Esophageal Motility in Scleroderma Patients ? Preliminary Results

Tu1249 – Autologous Haematopoetic Stem Cell Transplant (HSCT) May Improve Esophageal Motility in Scleroderma Patients ? Preliminary Results

CORRECTION: A type 2 diabetes mellitus patient was successfully treated by autologous bone marrow-derived stem cell transplantation: A case report

In the previous publication with title ”A type 2 diabetes mellitus patient was successfully treated by autologous bone marrow-derived stem cell transplantation: A case report”1, page 2968, in the Table 1, the unit for fasting blood glucose and blood glucose 2 hours after meals is mg/dL; however, the corrected unit for fasting blood glucose and blood glucose 2 hours after meal is mmol/L.

Growth of colorectal liver metastases is not accelerated by intraportal administration of stem cells after portal vein embolization

Future liver remnant volume (FLRV) is acrucial factor impacting resectability of colorectal liver metastases (CLM). In case of low FLRV, augmentation can be done by performing portal vein embolization (PVE). However, there is arisk of progression of CLM between PVE and resection. Intraportal application of autologous hematopoietic stem cells (HSC) is apossibility to accelerate the growth of FLRV. The effect of thus applied SC on CLM progression still remains unclear, though. 63 patients underwent PVE between 2003 and 2015. In 20 patients aproduct with HSC was applied intraportally on the first day after PVE (PVE HSC group). HSC were gained from peripheral blood (10 patients) or bone marrow (10 patients). FLRV and volume of liver metastases (VLM) were evaluated by CT volumetry. The gained data were statistically evaluated in relation to the disease free interval (DFI), overall survival (OS), achievement of CLM resectability and progression of extrahepatic metastases. We compared the PVE HSC group with the group of patient undergoing simple PVE. No significant difference in FLRV and VLM growth was observed between the study groups. The percentage of exploratory laparotomies was smaller in the group with PVE and HSC application. Patients with simple PVE had asignificantly higher incidence of extrahepatic metastases during follow up. We did not observe any significant differences in DFI and OS between the groups. HSC application did not accelerate CLM growth in comparison with PVE alone. PVE and HSC application had ahigher percentage of patients undergoing liver resection and alower incidence of extrahepatic metastases.

Analysis of clinical efficacy and safety of local radiotherapy in children with stage IV high-risk neuroblastoma

Objective To retrospectively analyze the clinical efficacy, safety and influencing factors of radiotherapy in children with stage Ⅳ high-risk neuroblastoma (HR-NB). Methods A total of 120 children with HR-NB who were diagnosed and treated with local radiotherapy according to the BCH-HR-NB-2007 protocol in the Oncology Department of Beijing Children′s Hospital from January 2014 to December 2017 were enrolled. Among them, 56 children were male and 64 female with a median age of 43 months (9-148 months). The treatment protocol consisted of 4 cycles of CAV chemotherapy, 3 cycles of CVP chemotherapy, surgical resection after 4 cycles, autologous hematopoietic stem cell transplantation after 7 cycles, local radiotherapy at a dose of 15.0-30.6 Gy for 82 cases of primary tumors and 38 cases of primary and metastatic tumors, followed by 13 cis-retinoic acid as maintenance therapy. The entire treatment protocol endured for approximately 18 months. Results The median follow-up time was 21 months. The 3-year local control rate was 84.4%. Before radiotherapy, the 3-year event-free survival rate was 78.4% in children without metastases, significantly higher compared with 30.4% in the residual group (P=0.003). The 3-year event-free survival rate was 66.1% in patients who underwent radiotherapy within 6 months after surgery, significantly higher than 50.6% in their counterparts receiving radiotherapy at 6 months or more after surgery (P=0.018). Among the children with residual metastases before radiotherapy, the progression rate in children who did not receive radiotherapy was 66.6%, significantly higher compared with 20.0% in those receiving radiotherapy (P=0.001). All patients had no radiation-related adverse reactions in the liver, kidney and heart, etc. The incidence rate of grade Ⅲ-IV myelosupression was 24.5% at 1 week post-radiotherapy, and 8% at 2 weeks after radiotherapy. Conclusions Radiotherapy yields definite clinical efficacy in the local control of children with stage Ⅳ HR-NB. Early radiotherapy after surgery and radiotherapy for the metastatic lesions can improve the clinical prognosis. No vital organ injuries are observed during the short-term follow-up. At 2 weeks after radiotherapy, the myelosupression is gradually restored. Key words: Neuroblastoma/radiotherapy; Neuroblastoma/chemotherapy; Prognosis

Efficacy of Different Doses of Human Autologous Adult Bone Marrow Stem Cell Transplantation on Angiogenesis in an Immune Deficient Rat Model with Hind Limb Ischemia

Efficacy of Different Doses of Human Autologous Adult Bone Marrow Stem Cell Transplantation on Angiogenesis in an Immune Deficient Rat Model with Hind Limb Ischemia

Invasive aspergillosis in children and adolescents with solid tumors: clinical cases and registry analysis

We presented two cases of invasive aspergillosis (IA) in children with solid tumors, data of IA patients register, and a literature review. In theregister of patients with IA (1997–2018), we found 57 patients with IA from 0 to 18 years. It was established that the number of patients with solid tumors was 15.7 %. Background diseases were: central nervous system tumors – 33.5 %, neuroblastoma – 33.5 %, osteosarcoma – 11.0 %, Wilms tumor – 11.0 %, hemangioblastoma – 11.0 %. Chemotherapy-induced neutropenia was reported in 100 % of IA cases in children and adolescents with solid tumors. The additional risk factors were treatment in intensive care unit – 22.2 %, high-dose chemotherapy with autologous hematopoietic stem cell transplantation – 22.2 %, concomitant bacterial infection – 33.0 %. Surgical intervention for the underlying disease was performed in 77.7 % of patients. The most common clinical site of IA was the lungs – 88.9 %. The predominant clinical sign was fever – 66.7 %, cough and respiratory failure were seen less frequently – 33.4 % and33.4 %, respectively. The etiologicalagents of IA were Aspergillus fumigatus – 33.3 %, Aspergillus nidulans – 33.3 % and Aspergillus ustus – 33.3 %. 88.9 % of patients received antimycotic therapy, voriconazole predominantly – 66.7 %. Combination therapy was used in 33.3 % of patients. The overall 12-week survival in children and adolescents with IA in case of solid tumors was 77.8 %.

Alemtuzumab induced thyrotoxicosis in a patient undergoing autologous haematopoietic stem cell transplant for multiple sclerosis

Alemtuzumab induced thyrotoxicosis in a patient undergoing autologous haematopoietic stem cell transplant for multiple sclerosis

Evaluation of Cilia Function in Rat Trachea Reconstructed Using Collagen Sponge Scaffold Seeded with Adipose Tissue-Derived Stem Cells.

The tracheal lumen is essential for conducting air to the lung alveoli and for voice production. However, patients with severe tracheal stenosis and malignant tumors invading the trachea often require tracheal resection. Recently, various reported tissue engineering methods for tracheal reconstruction show that regeneration of ciliated epithelium in the reconstructed areas, as well as preservation of the luminal structure is possible. However, only few studies report on the mucociliary transport function in reconstructed tracheae. We investigated mucociliary transport function within rat tracheal epithelium, reorganized after autologous adipose tissue-derived stem cell (ASC) transplantation. Rat ASCs were expanded in culture, and then seeded in a collagen sponge, which was physically supported with a polypropylene framework. The ASC-seeded collagen sponge was transplanted into the rat tracheal defect. We then examined the motility and transport function of cilia generated in the transplanted area using ciliary beat frequency (CBF) and microsphere movement analyses. Our data suggested that autologous ASC transplantation promoted ciliogenesis, consistent with previous reports. The CBF analysis revealed that motility of the cilia generated in the ASC group was comparable to that observed in the normal rat tracheal epithelium. Transport function in the ASC group was higher than that in the control group. These data suggested that autologous ASC transplantation increased ciliated cells in the reconstructed area without significantly disrupting cilia motility, thereby promoting transport function regeneration. Autologous ASC transplantation is expected to be beneficial in morphological and functional regeneration of tracheal epithelium. Anat Rec, 303:471-477, 2020. © 2019 American Association for Anatomy.