Autologous Cell Transplantation Research Articles

Overcoming Graft Rejection in Induced Pluripotent Stem Cell-Derived Inhibitory Interneurons for Drug-Resistant Epilepsy.

Cell-based therapies for drug-resistant epilepsy using induced pluripotent stem cell-derived inhibitory interneurons are now in early-phase clinical trials, building on findings from trials in Parkinson's disease (PD) and Huntington's disease (HD). Graft rejection and the need for immunosuppressive therapy post-transplantation pose potential barriers to more epilepsy patients becoming potential candidates for inhibitory interneurons transplantation surgery. The present literature review weighs the evidence for and against human leukocyte antigen (HLA)-mediated graft rejection in PD and HD and examines the potential advantages and drawbacks to five broad approaches to cell-based therapies, including autologous cell culture and transplantation, in vivo reprogramming of glial cells using viral vectors, allogeneic transplantation using off-the-shelf cell lines, transplantation using inhibitory interneurons cultured from HLA-matched cell lines, and the use of hypoimmunogenic-induced pluripotent stem cell-derived inhibitory interneurons. The impact of surgical technique and associated needle trauma on graft rejection is also discussed. Non-systematic literature review. While cell-based therapies have enjoyed early successes in treating a host of central nervous system disorders, the immunologic reaction against surgical procedures and implanted materials has remained a major obstacle. Adapting cell-based therapies using iPSC-derived inhibitory interneurons for epilepsy surgery will similarly require surmounting the challenge of immunogenicity.

Assessment of a nutritional status of patients qualified for autologous and allogeneic heamatopoietic cell transplantation

Assessment of a nutritional status of patients qualified for autologous and allogeneic heamatopoietic cell transplantation

Surgical Technique for Oral Mucosa Harvesting in Autologous Cultivated Oral Mucosal Epithelial Cell Transplantation for Ocular Surface Disorders.

Ex vivocultivated oral mucosal epithelial cell transplantation (COMET) was first introduced in Japan in June 2021. This technique is used to treat limbal stem cell deficiency (LSCD). This article provides a detailed description of one of the most critical steps in COMET, which is the harvesting of oral mucosa, along with accompanying videos. The samples harvested using this method were successfully cultured into cell sheets, which were then used in surgical procedures without complications.

Comparison between USPIOs and SPIOs for Multimodal Imaging of Extracellular Vesicles Extracted from Adipose Tissue-Derived Adult Stem Cells.

Adipose tissue-derived adult stem (ADAS) cells and extracellular vesicle (EV) therapy offer promising avenues for treating neurodegenerative diseases due to their accessibility and potential for autologous cell transplantation. However, the clinical application of ADAS cells or EVs is limited by the challenge of precisely identifying them in specific regions of interest. This study compares two superparamagnetic iron oxide nanoparticles, differing mainly in size, to determine their efficacy for allowing non-invasive ADAS tracking via MRI/MPI and indirect labeling of EVs. We compared a USPIO (about 5 nm) with an SPIO (Resovist®, about 70 nm). A physicochemical characterization of nanoparticles was conducted using DLS, TEM, MRI, and MPI. ADAS cells were labeled with the two nanoparticles, and their viability was assessed via MTT assay. MRI detected labeled cells, while TEM and Prussian Blue staining were employed to confirm cell uptake. The results revealed that Resovist® exhibited higher transversal relaxivity value than USPIO and, consequently, allows for detection with higher sensitivity by MRI. A 200 µgFe/mL concentration was identified as optimal for ADAS labeling. MPI detected only Resovist®. The findings suggest that Resovist® may offer enhanced detection of ADAS cells and EVs, making it suitable for multimodal imaging. Preliminary results obtained by extracting EVs from ADAS cells labeled with Resovist® indicate that EVs retain the nanoparticles, paving the way to an efficient and multimodal detection of EVs.

Bone Marrow and Peripheral Blood Mononuclear Cell Phenotype Changes after Cultivation and Autologous Infusion in Patients with Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is a condition affecting the liver and immune system. In this study, the impact of autologous bone marrow-derived mononuclear cell (BM-MNC) transplantation on PBC patients was investigated. Sixteen eligible PBC patients participated at the National Scientific Medical Center in Astana, Kazakhstan, between 2017 and 2022, and BM-MNCs were harvested from their anterior iliac crest. After isolating and cultivating the BM-MNCs, they were infused back into the patient's peripheral veins. Changes in BM-MNC and peripheral blood mononuclear cell (PB-MNC) phenotypes were assessed before and after a 24-hour cultivation period and 72 hours post-transplantation. We monitored liver function parameters over 6-month intervals and conducted flow cytometry analysis to assess CD markers on BM-MNCs before and after cultivation and PB-MNCs before and after transplantation. Statistical analysis included the Friedman test for liver parameters and the Wilcoxon signed-rank test for BM-MNC and PB-MNC comparisons. Our findings revealed significant reductions in liver function tests after multiple transplantations. Flow cytometry analysis before and after a 24-hour culture and autologous BM-MNC infusion revealed the expansion of specific cell populations, with significant increases in CD3+, CD4+, CD16+, CD20+, CD25+, CD34+, CD105+, CD73+, СD117+, and CD34+populations, while CD4+25+, CD34+105+, and CD4+FOXP3+ populations decreased. Interestingly, a contradictory finding was observed with a decrease in bone marrow CD34+105+ cell lines (P=0.03) alongside an increase in peripheral CD34+105+ population (P=0.03). In summary, our study shows that BM-MNC transplantation in PBC patients leads to changes in immune cell populations and liver function. These findings suggest potential therapeutic applications of BM-MNC transplantation in managing PBC and offer insights into the dynamics of immune cells associated with this treatment approach.

Comparison of single day versus two-and three- day fractionated infusion of peripheral stem cells in autologous transplantation

Bacgroun/Purpose: The aim of this study was to investigate the safety, difference in duration of engraftment and relapse rates between autologous transplant patients who had their stem cell infusions during a single day or multiple days. Methods: In this retrospective study the clinical data of 77 ASCT patients from a single center,30 of whom were transplanted in fractionated infusions were investigated. Duration of engraftment, side effects during the transplant, PFS and OS data of the two groups was compared. Results: There was no statistical difference between single day and fractionated infusion patients regarding neutrophil engraftment, toxic side effects, PFS, OS and relapse rate at 18 months. Platelet engraftment was delayed for one day in the fractionated group, which did not cause prolonged hospitalization. The transplant patients who had multiple day infusion had similar engraftment duration despite their lower average CD34+ cell counts. Conclusion: Fractionated infusions lead to similar engraftment duration to single day infusion for ASCT. The higher CFU cell number seen in the poorly mobilized patients may have a key role in the adequate engraftment. The fractionated infusion approach for such patients was feasible, safe and no increase of the disease relapse was observed with this procedure.

A Novel CRISPR-Cas9 Strategy to Target DYSTROPHIN Mutations Downstream of Exon 44 in Patient-Specific DMD iPSCs.

Mutations in the DMD gene cause fatal Duchenne Muscular Dystrophy (DMD). An attractive therapeutic approach is autologous cell transplantation utilizing myogenic progenitors derived from induced pluripotent stem cells (iPSCs). Given that a significant number of DMD mutations occur between exons 45 and 55, we developed a gene knock-in approach to correct any mutations downstream of exon 44. We applied this approach to two DMD patient-specific iPSC lines carrying mutations in exons 45 and 51 and confirmed mini-DYSTROPHIN (mini-DYS) protein expression in corrected myotubes by western blot and immunofluorescence staining. Transplantation of gene-edited DMD iPSC-derived myogenic progenitors into NSG/mdx4Cv mice produced donor-derived myofibers, as shown by the dual expression of human DYSTROPHIN and LAMIN A/C. These findings further provide proof-of-concept for the use of programmable nucleases for the development of autologous iPSC-based therapy for muscular dystrophies.

Neural Stem Cell-based Regenerative Therapy: A New Approach to Diabetes Treatment.

Diabetes mellitus (DM) is the most common metabolic disorder that occurs due to the loss, or impaired function of insulin-secreting pancreatic beta cells, which are of two types - type 1 (T1D) and type 2 (T2D). To cure DM, the replacement of the destroyed pancreatic beta cells of islet of Langerhans is the most widely practiced treatment. For this, isolating neuronal stem cells and cultivating them as a source of renewable beta cells is a significant breakthrough in medicine. The functions, growth, and gene expression of insulin-producing pancreatic beta cells and neurons are very similar in many ways. A diabetic patient's neural stem cells (obtained from the hippocampus and olfactory bulb) can be used as a replacement source of beta cells for regenerative therapy to treat diabetes. The same protocol used to create functional neurons from progenitor cells can be used to create beta cells. Recent research suggests that replacing lost pancreatic beta cells with autologous transplantation of insulin-producing neural progenitor cells may be a perfect therapeutic strategy for diabetes, allowing for a safe and normal restoration of function and a reduction in potential risks and a long-term cure.

Autologous cell transplantation for treatment of colorectal aganglionosis in mice

Neurointestinal diseases cause significant morbidity and effective treatments are lacking. This study aimes to test the feasibility of transplanting autologous enteric neural stem cells (ENSCs) to rescue the enteric nervous system (ENS) in a model of colonic aganglionosis. ENSCs are isolated from a segment of small intestine from Wnt1::Cre;R26iDTR mice in which focal colonic aganglionosis is simultaneously created by diphtheria toxin injection. Autologous ENSCs are isolated, expanded, labeled with lentiviral-GFP, and transplanted into the aganglionic segment in vivo. ENSCs differentiate into neurons and glia, cluster to form neo-ganglia, and restore colonic contractile activity as shown by electrical field stimulation and optogenetics. Using a non-lethal model of colonic aganglionosis, our results demonstrate the potential of autologous ENSC therapy to improve functional outcomes in neurointestinal disease, laying the groundwork for clinical application of this regenerative cell-based approach.

Long Term Remission of Capillary Leak Syndrome Associated with Monoclonal Gammopathy with Progression to Multiple Myeloma After Autologous Stem Cell Transplantation: a Case Report and Review of the Literature.

Clarkson's disease is a very rare entity characterised by acute episodes of systemic oedema and severe hypotension associated with paraproteinaemia. Its classical treatment relies on methylxanthine combined with terbutaline. Although this prophylactic therapy reduces the mortality rate, relapses are frequent. Eighty percent of patients with Clarkson's disease present with monoclonal gammopathy of unknown significance (MGUS). The risk of progression to multiple myeloma is 1% per year. Here, we present a 49-year-old woman who suffered multiple such episodes requiring treatment in the intensive care unit. Treatment with terbutaline and theophylline was ineffective. She was diagnosed with multiple myeloma (MM) 8 years after the first of these acute episodes. Antimyeloma treatment with bortezomib and dexamethasone was started, followed by autologous haemopoietic transplantation, with no further acute episodes since then. Our case is, to our knowledge, unique because eradication of MM was followed by complete disappearance of acute episodes of capillary leakage. Our case report is also the first to support the use of bortezomib and dexamethasone in this setting. Furthermore, autologous peripheral blood progenitor cell transplantation consolidated the MM stringent complete remission achieving a very long progression-free survival (> 11 years) of both MM and Clarkson's disease.

Transplantation of autologous mesenchymal stromal cells in complete cervical spinal cord injury: a pilot study.

Spinal cord injury (SCI) is a serious condition that can lead to partial or complete paraplegia or tetraplegia. Currently, there are few therapeutic options for these conditions, which are mainly directed toward the acute phase, such as surgical intervention and high-dose steroid administration. Mesenchymal stromal cells (MSC) have been shown to improve neurological function following spinal cord injury. The aim of the study was to evaluate the safety, feasibility, and potential efficacy of MSC transplantation in patients with cervical traumatic SCI. We included seven subjects with chronic traumatic SCI (> 1 year) at the cervical level, classified as American Spinal Cord Injury Association impairment scale (AIS) grade A. Subjects received two doses of autologous bone marrow derived MSC, the first by direct injection into the lesion site after hemilaminectomy and the second three months later by intrathecal injection. Neurologic evaluation, spinal magnetic resonance imaging (MRI), urodynamics, and life quality questionnaires were assessed before and after treatment. Cell transplantation was safe without severe or moderate adverse effects, and the procedures were well tolerated. Neurological evaluation revealed discrete improvements in sensitivity below the lesion level, following treatment. Five subjects showed some degree of bilateral sensory improvement for both superficial and deep mechanical stimuli compared to the pretreatment profile. No significant alterations in bladder function were observed during this study. Transplantation of autologous MSC in patients with chronic cervical SCI is a safe and feasible procedure. Further studies are required to confirm the efficacy of this therapeutic approach. https://clinicaltrials.gov/study/NCT02574572, identifier NCT02574572.

Robotic total pancreatectomy with autologous islet cell transplant: safety evaluation and outcomes

Robotic total pancreatectomy with autologous islet cell transplant: safety evaluation and outcomes

Robotic total pancreatectomy with autologous islet cell transplant: safety evaluation and outcomes

Robotic total pancreatectomy with autologous islet cell transplant: safety evaluation and outcomes

Vitiligo and surgical treatment

Objective: Initial comments on the effectiveness of surgical treatment of vitiligoResearch subjects and methods: A prospective study on 12 cases of vitiligo that were successfully treated with autologous pigment cell transplant surgery. Research period from September 2018 to October 2022 at the Center for Plastic Surgery, Surgery & Regeneration - Le Huu Trac National Burn HospitalResults: 12 patients with an average age of 29, with vitiligo in several locations on the body, received pigment-containing cell transplant surgery. The graft adheres well, ensuring good coverage and assimilating the color of the vitiligo skin area with the surrounding healthy skin after about 12 months.Conclusion: Pigment graft surgery is one of the effective methods of treating vitiligo and can be applied to large areas of the diseased skin.

Implanting mechanically reprogrammed fibroblasts for aged tissue regeneration and wound healing.

Cell-based therapies are essential for tissue regeneration and wound healing during aging. Autologous transplantation of aging cells is ineffective due to their increased senescence and reduced tissue remodeling capabilities. Alternatively, implanting reprogrammed aged cells provides unique opportunities. In this paper, we demonstrate the implantation of partially reprogrammed aged human dermal fibroblasts into invitro aged skin models for tissue regeneration and wound healing. The partially reprogrammed cells were obtained using our previously reported, highly efficient mechanical approach. Implanted cells showed enhanced expression of extracellular matrix proteins in the large area of aged tissue. In addition, the implanted cells at wound sites showed increased extracellular matrix protein synthesis and matrix alignment. Transcriptome analysis, combined with chromatin biomarkers, revealed these implanted cells upregulated tissue regeneration and wound healing pathways. Collectively our results provide a novel, nongenetic, partial reprogramming of aged cells for cell-based therapies in regenerative medicine.

Autologous Airway Basal Cell Transplantation Alleviates Airway Epithelium Defect in Recurrent Benign Tracheal Stenosis.

Airway epithelium defects are a hallmark of recurrent benign tracheal stenosis (RBTS). Reconstructing an intact airway epithelium is of great importance in airway homeostasis and epithelial wound healing and has great potential for treating tracheal stenosis. An experimental study was conducted in canines to explore the therapeutic effect of autologous basal cell transplantation in restoring airway homeostasis. First, airway mucosae from human patients with recurrent tracheal stenosis were analyzed by single-cell RNA sequencing. Canines were then randomly divided into tracheal stenosis, Stent, Stent + Cells, and Stent + Cells + Biogel groups. Autologous airway basal cells of canines in the Stent + Cells and Stent + Cells + Biogel groups were transplanted onto the stenotic airway after modeling. A biogel was coated on the airway prior to basal cell transplantation in the Stent + Cells + Biogel group. After bronchoscopic treatments, canines were followed up for 16 weeks. Single-cell RNA sequencing demonstrated packed airway basal cells and an absence of normal airway epithelial cells in patients with RBTS. Autologous airway basal cell transplantation, together with biogel coating, was successfully performed in the canine model. Follow-up observation indicated that survival time in the Stent + Cells + Biogel group was significantly prolonged, with a higher (100%) survival rate compared with the other groups. In terms of pathological and bronchoscopic findings, canines that received autologous basal cell transplantation showed a reduction in granulation hyperplasia as well as airway re-epithelialization with functionally mature epithelial cells. Autologous airway basal cell transplantation might serve as a novel regenerative therapy for airway re-epithelialization and inhibit recurrent granulation hyperplasia in benign tracheal stenosis.

SAT502 Choristoma: A Very Rare Cause of Thyroid Nodule. Clinical Case and Literature Review

Abstract Disclosure: J. Rocha: None. R. Moiteiro da Cruz: None. M. Alexandre: None. A. Gomes: None. D. López-Presa: None. M.J. Bugalho: None. Introduction: A choristoma is a well delimitated benign lesion formed by normal tissue in an unusual location. Choristomas are rare lesions that are mainly reported in the eye, tongue or ears. The etiology of the choristoma is not well established but congenital defects in cell migration and exposure to chronic inflammation are two of the suggested hypothesys. Diagnosis is made after surgical removal of the mass, usually with no other associated abnormalities. To our knowledge, to this day there is only one other case of thyroid choristoma described in literature. Clinical case: A 70-year-old man presented to the emergency department with hyperglycemia, polydipsia and polyuria. Personal history was notable for non-Hodgkin lymphoma in remission after stem cell autologous transplant, currently under high dose prednisolone treatment due to sudden cervical enlargement. Cervical imaging with CT scan showed a 47mm hypodense nodule of the right thyroid lobe. The patient was refered to an Endocrinology appointment.Thyroid function was normal, with normal serum calcitonin and negative anti TPO and antiTG antibodies. Fine-needle aspiration biopsy was notable for folicular lesion of undetermined significance. During the following weeks there was a noticeable thyroid enlargement causing positional dyspnoea and dysphonia. Ultrassound revealed a 73mm nodule of the right lobe, predominantly cystic and isoechoic in the solid regions. At this point the patient underwent total thyroidectomy without complications.Histopathological examination revealed a choristoma composed of cysts lined by squamous epitelium, smooth muscle bundles, mature adipose tissue, areas of calcification and ossification and extramedullary hematopoiesis; there were also signs of old and recent haemorrhage and foreign body granulomas. No cytological atypia or tumoral necrosis were found. Conclusion: Thyroid choristomas are extremely rare entities. Unlike the previously described case our patient had a rapid growth of the cervical mass. This case is specially relevant due to its clinical course, existing comorbidities and rarity of the final diagnosis. Presentation Date: Saturday, June 17, 2023

Intravenous transplantation of bone marrow-derived mesenchymal stromal cells in patients with multiple sclerosis, a phase I/IIa, double blind, randomized controlled study.

Multiple sclerosis (MS) is a progressive, demyelinating neurodegenerative disease of the central nervous system. MS is immune-mediated and leads to disability especially in young adults. Even though 18 MS therapy drugs were approved, they slightly inhibit disease progression and do not induce regeneration and repair in the nervous system. Mesenchymal stromal cells (MSCs) have emerged as a new therapeutic modality in regenerative medicine and tissue engineering due to their immunomodulation and bio regenerative properties. We have designed a randomized, controlled clinical trial to assess safety and possible efficacy of MSC application in MS patients. Twenty-one MS patients were enrolled. Patients were allocated in two distinct groups: treatment group, which received systemic transplantation of autologous bone marrow-derived MSCs, and control group, which received placebo at the first injections. Patients in control group received MSCs at the second injection while the treatment group received placebo. All the patients were followed for 18 months. Follow-ups included regular visits, laboratory evaluation, and imaging analysis. Control patients received MSCs six month after treatment group. No severe immediate or late adverse events were observed in both groups after interventions. We did not find any significant differences in the rate of relapses, Expanded Disability Status Scale (EDSS) score, cognitive condition, Magnetic Resonance Imaging (MRI) findings, or any biomarkers of cerebrospinal fluid between the two groups and in each group before and after cell infusion. Transplantation of autologous bone marrow-derived mesenchymal stromal cells is safe and feasible. The efficacy of transplantation of these cells should be evaluated through designing randomized clinical trials with larger sample sizes, different administration routes, other cell types (allogeneic adipose derived MSCs, allogeneic Wharton's jelly derived MSCs …), repeated injections, and longer follow-up periods.

Efficacy of autologous dermal sheath cup cell transplantation in male and female pattern hair loss: A Single-Arm, Multi-Center, phase III equivalent clinical study.

A previous, proof-of-concept clinical study suggested that dermal sheath cup cell injections into the affected areas of male/female pattern hair loss (PHL) may have some amelioratory effects, the clinical efficacy of which needs further examination. A phase III equivalent clinical study was conducted to further probe the therapeutic potential of this novel approach and verify its safety and efficacy in improving the appearance of PHL. Thirty-six participants with PHL were injected with dermal sheath cup cell harvested from non-affected occipital hair follicles twice in quarterly intervals. Global photographic assessment and phototrichogram were performed in a blinded manner. Patient-reported outcomes were assessed for 12 months. On global photographic assessment, 30% of the participants showed improvement. The analysis of phototricogram data detected the increases in the cumulative hair diameter, hair cross-sectional area, and mean hair diameter of 107.6 ± 152.6 μm/cm2 , 13069.1 ± 10960.7 μm2 /cm2 , and 0.9 ± 0.9 μm (ratios vs. baseline: +1.4%, +3.4%, and +2.2%), respectively. The female and high terminal hair ratio groups achieved better improvement. Of the total participants, 62.9% noted some degree of improvement. No serious adverse events were detected. This novel approach exhibited visible effects while ensuring safety and patient satisfaction. Therefore, it holds promise as a possible therapeutic option for treating PHL, especially in women.

Autologous cell transplant as a treatment for stable segmental vitiligo: a systematic review.

This systematic review provides a comprehensive analysis of the efficacy of autologous cell transplant as a therapeutic approach for stable segmental vitiligo. Vitiligo poses significant challenges for healthcare professionals in terms of treatment selection. Autologous cell transplant has emerged as a promising modality for managing vitiligo, with cultured and noncultured transplants being considered when determining the patient's treatment approach. There is little knowledge and literature on the subject, so we analyze the different studies. Using online medical literature databases and the PRISMA guidelines, six out of 60 articles met the acceptance criteria to be analyzed, emphasizing the lack of current literature on this subject. Autologous cell transplant achieves excellent pigmentation rates for many body parts. We found that cultivated cells had better results than noncultivated ones. Both types of treatments could pigment 80% or more where needed. This review highlights the importance of autologous cell transplant as a new and reliable tool for the treatment of stable segmental vitiligo, cultured transplants being the most effective. By employing autologous cell transplant, the repigmentation rate is notably high and consistently achievable. Although its cost and logistical complexities hinder the current accessibility to this therapy, efforts are being made to enhance its availability, and its scope is expected to expand further. More studies are needed to understand this therapy method in other kinds of vitiligo.