Use of platelet rich plasma for skin rejuvenation.

OBJECTIVE: Platelet-rich plasma (PRP) is recognized as a safe and effective therapy for regenerative skin healing and rejuvenation, utilizing autologous blood enriched with various growth factors. This review aims to assess the efficacy of PRP treatments for skin rejuvenation. METHODS: Keywords such as "platelet-rich plasma," "rejuvenation," "skin aging," and "wrinkles" were queried on Ovid, PubMed, and MEDLINE to identify pertinent studies on PRP treatment for skin rejuvenation. RESULTS: Analysis revealed that PRP treatment led to significant enhancements in multiple facial parameters after one to three sessions. Improvements were noted in skin pore size, texture, wrinkle reduction, pigmented spots, collagen density, hyaluronic acid levels, and protection against ultraviolet damage. Combining PRP with hyaluronic acid demonstrated a synergistic effect, particularly enhancing skin elasticity in patients with lower body mass index and firmness in individuals aged 50s and 60s. Incorporating both physical and biometric data for assessment proved superior to relying solely on physical observations for evaluating subtle skin quality and structural changes. CONCLUSION: This study underscores the efficacy of PRP monotherapy for skin rejuvenation and emphasizes the necessity of standardizing PRP preparation protocols in future investigations. Heightened awareness and advancements in technology have contributed to the emergence of higher-quality, less biased studies supporting PRP as a reliable and safe therapeutic option for skin rejuvenation.

A review of fetal cell lines used during drug development: Focus on COVID-19 vaccines, transplant medications, and biologics.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: The recent coronavirus disease 2019 (COVID-19) pandemic and vaccine mandates have increased the number of patient questions related to how fetal cell lines are used during drug development and final manufacturing. This article describes our literature search and review of COVID-19 vaccines, transplant medications, and biologics whose development included use of fetal cell lines. SUMMARY: A detailed literature search was conducted to identify the common fetal cell lines used in COVID-19 vaccine development; the two most prevalent fetal cell lines identified were HEK-293 and PER.C6. Subsequent literatures searches were conducted to identify transplant medications and biologics whose development included use of the HEK-293 or PER.C6 cell lines. For the COVID-19 vaccines, only the viral vector vaccine by Janssen was found to contain proteins produced by PER.C6 in the final preparation administered to patients, and Novavax is the only vaccine for which fetal cell lines were not directly involved in any portion of drug development. For transplant medications, many medications were studied in fetal cell lines in postmarketing studies after Food and Drug Administration approval; however, none of these medications contained fetal cells or would expose a patient to a fetal cell line. Many new biologics and cellular therapies for genetic diseases and malignancies have been directly developed from HEK-293 fetal cells or contain proteins produced directly from fetal cell lines. CONCLUSION: There were very few drugs reviewed that were found to contain HEK-293 or PER.C6 fetal cells or proteins derived directly from fetal cell lines; however, use of fetal cell lines in biologics and gene therapies will continue to increase. Healthcare providers should be mindful of patients' beliefs while also correcting common misconceptions about how these fetal cell lines are used throughout drug development and manufacturing.

Melatonin as an immunomodulator in CD19-targeting CAR-T cell therapy: managing cytokine release syndrome.

BACKGROUND: Chimeric antigen receptor CAR-T cell therapies have ushered in a new era of treatment for specific blood cancers, offering unparalleled efficacy in cases of treatment resistance or relapse. However, the emergence of cytokine release syndrome (CRS) as a side effect poses a challenge to the widespread application of CAR-T cell therapies. Melatonin, a natural hormone produced by the pineal gland known for its antioxidant and anti-inflammatory properties, has been explored for its potential immunomodulatory effects. Despite this, its specific role in mitigating CAR-T cell-induced CRS remains poorly understood. METHODS: In this study, our aim was to investigate the potential of melatonin as an immunomodulatory agent in the context of CD19-targeting CAR-T cell therapy and its impact on associated side effects. Using a mouse model, we evaluated the effects of melatonin on CAR-T cell-induced CRS and overall survival. Additionally, we assessed whether melatonin administration had any detrimental effects on the antitumor efficacy and persistence of CD19 CAR-T cells. RESULTS: Our findings demonstrate that melatonin effectively mitigated the severity of CAR-T cell-induced CRS in the mouse model, leading to improved overall survival outcomes. Remarkably, melatonin administration did not compromise the antitumor effectiveness or persistence of CD19 CAR-T cells, indicating its compatibility with therapeutic goals. These results suggest melatonin's potential as an immunomodulatory compound to alleviate CRS without compromising the therapeutic benefits of CAR-T cell therapy. CONCLUSION: The study's outcomes shed light on melatonin's promise as a valuable addition to the existing treatment protocols for CAR-T cell therapies. By attenuating CAR-T cell-induced CRS while preserving the therapeutic impact of CAR-T cells, melatonin offers a potential strategy for optimizing and refining the safety and efficacy profile of CAR-T cell therapy. This research contributes to the evolving understanding of how to harness immunomodulatory agents to enhance the clinical application of innovative cancer treatments.

Endochondral Repair of Jawbone Defects Using Periosteal Cell Spheroids.

Recapitulation of the natural healing process is receiving increasing recognition as a strategy to induce robust tissue regeneration. Endochondral ossification has been recognized as an essential reparative approach in natural jawbone defect healing. However, such an approach has been overlooked in the recent development of cell-based therapeutics for jawbone repair. Therefore, this study aimed to explore a bioinspired stem cell-based strategy for jawbone repair by mimicking the mesenchymal condensation of progenitor cells during the early endochondral ossification process. For this purpose, passage 3 of jawbone periosteum-derived cells (jb-PDCs) was cultured in our previously reported nonadherent microwells (200 µm in diameter, 148 µm in depth, and 100 µm space in between) and self-assembled into spheroids with a diameter of 96.4 ± 5.8 µm after 48 h. Compared to monolayer culture, the jb-PDC spheroids showed a significant reduction of stemness marker expression evidenced by flow cytometry. Furthermore, a significant upregulation of chondrogenic transcription factor SOX9 in both gene and protein levels was observed in the jb-PDC spheroids after 48 h of chondrogenic induction. RNA sequencing and Western blotting analysis further suggested that the enhanced SOX9-mediated chondrogenic differentiation in jb-PDC spheroids was attributed to the activation of the p38 MAPK pathway. Impressively, inhibition of p38 kinase activity significantly attenuated chondrogenic differentiation jb-PDC spheroids, evidenced by a significant decline of SOX9 in both gene and protein levels. Strikingly, the jb-PDC spheroids implanted in 6- to 8-wk-old male C57BL/6 mice with critical-size jawbone defects (1.8 mm in diameter) showed an evident contribution to cartilaginous callus formation after 1 wk, evidenced by histological analysis. Furthermore, micro-computed tomography analysis showed that the jb-PDC spheroids significantly accelerated bone healing after 2 wk in the absence of exogenous growth factors. In sum, the presented findings represent the successful development of cell-based therapeutics to reengineer the endochondral bone repair process and illustrate the potential application to improve bone repair and regeneration in the craniofacial skeleton.

The effects of mesenchymal stromal cells and platelet-rich plasma treatments on cutaneous wound healing: ignoring the possibility of adverse events and side effects could compromise study results.

Common medical events may be associated with decreased immunologic activity and dysregulation of functional epithelial and neuronal tissues caused by growth factors and vesicle secretion by stem and somatic cells. Systemic injection of MSCs has been shown to reduce the immune response mainly through paracrine mechanisms, but some points related to the possibility of adverse events and side effects should be clarified. Flow cytometry for at least 20 cell markers is crucial to assess cell senescence and overall cell viability. Thus, adverse events and unreasonable expectations from cell therapy can be prevented. We believe that by using the precision cell phenotyping kits in clinical trials, many undesirable side effects related to misconceptions about the origin of the cells can be avoided.

Pediatric Drug Development: Reviewing Challenges and Opportunities by Tracking Innovative Therapies.

The paradigm of pediatric drug development has been evolving in a "carrot-and-stick"-based tactic to address population-specific issues. However, the off-label prescription of adult medicines to pediatric patients remains a feature of clinical practice, which may compromise the age-appropriate evaluation of treatments. Therefore, the United States and the European Pediatric Formulation Initiative have recommended applying nanotechnology-based delivery systems to tackle some of these challenges, particularly applying inorganic, polymeric, and lipid-based nanoparticles. Connected with these, advanced therapy medicinal products (ATMPs) have also been highlighted, with optimistic perspectives for the pediatric population. Despite the results achieved using these innovative therapies, a workforce that congregates pediatric patients and/or caregivers, healthcare stakeholders, drug developers, and physicians continues to be of utmost relevance to promote standardized guidelines for pediatric drug development, enabling a fast lab-to-clinical translation. Therefore, taking into consideration the significance of this topic, this work aims to compile the current landscape of pediatric drug development by (1) outlining the historic regulatory panorama, (2) summarizing the challenges in the development of pediatric drug formulation, and (3) delineating the advantages/disadvantages of using innovative approaches, such as nanomedicines and ATMPs in pediatrics. Moreover, some attention will be given to the role of pharmaceutical technologists and developers in conceiving pediatric medicines.

New insights in application of mesenchymal stem cells therapy in tumor microenvironment: pros and cons.

Multipotent mesenchymal stem cells (MSCs) are widely accepted as a useful tool for cell-based therapy of various diseases including malignancies. The therapeutic effects of MSCs are mainly attributed to their immunomodulatory and immunosuppressive properties. Despite the promising outcomes of MSCs in cancer therapy, a growing body of evidence implies that MSCs also show tumorigenic properties in the tumor microenvironment (TME), which might lead to tumor induction and progression. Owing to the broad-spectrum applications of MSCs, this challenge needs to be tackled so that they can be safely utilized in clinical practice. Herein, we review the diverse activities of MSCs in TME and highlight the potential methods to convert their protumorigenic characteristics into onco-suppressive effects.

ICOS and OX40 tandem co-stimulation enhances CAR T-cell cytotoxicity and promotes T-cell persistence phenotype.

Chimeric Antigen Receptor (CAR) T-cell therapies have emerged as an effective and potentially curative immunotherapy for patients with relapsed or refractory malignancies. Treatment with CD19 CAR T-cells has shown unprecedented results in hematological malignancies, including heavily refractory leukemia, lymphoma, and myeloma cases. Despite these encouraging results, CAR T-cell therapy faces limitations, including the lack of long-term responses in nearly 50-70% of the treated patients and low efficacy in solid tumors. Among other reasons, these restrictions are related to the lack of targetable tumor-associated antigens, limitations on the CAR design and interactions with the tumor microenvironment (TME), as well as short-term CAR T-cell persistence. Because of these reasons, we developed and tested a chimeric antigen receptor (CAR) construct with an anti-ROR1 single-chain variable-fragment cassette connected to CD3ζ by second and third-generation intracellular signaling domains including 4-1BB, CD28/4-1BB, ICOS/4-1BB or ICOS/OX40. We observed that after several successive tumor-cell in vitro challenges, ROR1.ICOS.OX40ζ continued to proliferate, produce pro-inflammatory cytokines, and induce cytotoxicity against ROR1+ cell lines in vitro with enhanced potency. Additionally, in vivo ROR1.ICOS.OX40ζ T-cells showed anti-lymphoma activity, a long-lasting central memory phenotype, improved overall survival, and evidence of long-term CAR T-cell persistence. We conclude that anti-ROR1 CAR T-cells that are activated by ICOS.OX40 tandem co-stimulation show in vitro and in vivo enhanced targeted cytotoxicity associated with a phenotype that promotes T-cell persistence.

Application of the Yamanaka Transcription Factors Oct4, Sox2, Klf4, and c-Myc from the Laboratory to the Clinic.

The transcription factors Oct4, Sox2, Klf4, and c-Myc enable the reprogramming of somatic cells into induced pluripotent cells. Reprogramming generates newly differentiated cells for potential therapies in cancer, neurodegenerative diseases, and rejuvenation processes. In cancer therapies, these transcription factors lead to a reduction in the size and aggressiveness of certain tumors, such as sarcomas, and in neurodegenerative diseases, they enable the production of dopaminergic cells in Parkinson's disease, the replacement of affected neuronal cells in olivopontocerebellar atrophy, and the regeneration of the optic nerve. However, there are limitations, such as an increased risk of cancer development when using Klf4 and c-Myc and the occurrence of abnormal dyskinesias in the medium term, possibly generated by the uncontrolled growth of differentiated dopaminergic cells and the impairment of the survival of the new cells. Therefore, the Yamanaka transcription factors have shown therapeutic potential through cell reprogramming for some carcinomas, neurodegenerative diseases, and rejuvenation. However, the limitations found in the studies require further investigation before the use of these transcription factors in humans.

Extent of Tissue Washing Can Significantly Alter the Composition of Adipose-Derived Stromal Vascular Fraction Cell Preparations: Implications for Clinical Translation.

Stromal vascular fraction (SVF) cell preparations have recently attracted much interest as a form of autologous cell therapy. These heterogenous cell populations typically include some proportion of blood-derived cells (BDCs)-including both red blood cells (RBCs) and leukocytes (WBCs). The objectives of this paper were to evaluate the effects of tissue washing and hypotonic RBC lysis-separately and together-on BDC concentrations within SVF, and further to explore whether BDCs can confer detectable and modifiable effects on adipose-derived cell activity. Using various cell culture assays, flow cytometry and ELISA analysis of human-derived SVF preparations, we show that thorough washing of adipose tissue prior to enzymatic dissociation effectively removes RBCs from SVF preparations as well as standard lysis methods and significantly alters the type and relative quantities of WBCs. In addition, these studies demonstrate that potentially toxic RBC components are detectable for up to 1 week in cultures containing RBC lysate, but not those with intact RBCs, and, that culture-expanded cells proliferate significantly more in the presence of intact RBCs versus RBC lysis products or control media. Broadly, these data exemplify how different seemingly mundane tissue processing steps can significantly influence SVF identity/composition, purity, and potency. Based on the findings of this work, we propose that translational efforts in the field would benefit by a better understanding of the impact of RBCs, WBCs, and non-viable cells on the in vivo therapeutic activity of SVF therapies.

How to establish infrastructures to achieve more efficient regenerative medicine?

The field of regenerative medicine (RM) as an innovative technology has the ability to affect the healthcare system. It develops a variety of techniques through stem cell biology, genetics, bioengineering, biomaterial science, and tissue engineering to replace or restore the role of lost, disabled, or aging cells in the human body. However, the field's proficiency has still been underwhelming at the clinical trial level. This could be due to the innovation of such technologies, as well as their incredible nature. Therefore, managing the infrastructure framework for the safe and efficient application of the aforementioned field of science would help in the process of progress. In this context, the current review focuses on how to establish infrastructures for more effective RM.

Establishing Rationale for the Clinical Development of Cell Therapy Products: Consensus between Risk and Benefit.

Despite long-term research achievements, the development of cell therapy (CT) products remains challenging. This is because the risks experienced by the subject and therapeutic effects in the clinical trial stage are unclear due to the various uncertainties of CT when administered to humans. Nevertheless, as autologous cell products for systemic administration have recently been approved for marketing, CT product development is accelerating, particularly in the field of unmet medical needs. The human experience of CT remains insufficient compared with other classes of pharmaceuticals, while there are countless products for clinical development. Therefore, for many sponsors, understanding the rationale of human application of an investigational product based on the consensus and improving the ability to apply it appropriately for CT are necessary. Thus, defining the level of evidence for safety and efficacy fundamentally required for initiating the clinical development and preparing it using a reliable method for CT. Furthermore, the expertise should be strengthened in the design of the first-in-human trial, such as the starting dose and dose-escalation plan, based on a sufficiently acceptable rationale. Cultivating development professionals with these skills will increase the opportunity for more candidates to enter the clinical development phase.

Regeneración celular en los defectos óseos segmentarios

Introducción : Los defectos óseos segmentarios se producen por traumas de alta energía que ocasionan pérdida aguda de hueso, ocurren en forma subaguda durante el desbridamiento quirúrgico de una fractura expuesta y también pueden verse en casos crónicos como pseudoartrosis y osteomielitis, los que alteran la calidad de vida del paciente. Objetivo : Presentar un paciente con defecto óseo segmentario secundario a pseudoartrosis hipertrófica de húmero derecho de 6,3 cm. Caso clínico : Paciente masculino de 45 años de edad, raza blanca, sin antecedentes patológicos personales, que llega a nuestra consulta referido de otra institución de salud con diagnóstico de Pseudoartrosis hipertrófica de húmero derecho de tres años de evolución. Se realizó la técnica de inducción de membrana (Masquelet) la cual se combinó con la implantación de células madres adultas autólogas en el segundo tiempo quirúrgico. Se logró la consolidación ósea a las 12 semanas. Conclusiones: Dentro las variantes terapéuticas de los defectos óseos segmentarios se destaca la técnica de inducción de membrana que en combinación con el uso de la terapia celular constituye una opción prometedora, al necesitar un menor volumen de injerto, rápida consolidación además de una alternativa económica y de fácil elaboración sin gran complejidad tecnológica.

Introduction: Segmental bone defects are produced by high-energy traumas that cause acute bone loss, occur sub-acutely during surgical debridement of an exposed fracture, and can also be seen in chronic cases such as pseudarthrosis and osteomyelitis, drastically altering the quality of life of the patient. Objective: To present a patient with a segmental bone defect secondary to hypertrophic nonunion of the right humerus measuring 6.3 cm. Case report: A 45-year-old male patient, Caucasian, with no personal pathological history, who came to our office referred from another health institution with a diagnosis of hypertrophic pseudoarthrosis of the right humerus of 3 years of evolution. The membrane induction technique (Masquelet) is performed, which was combined with the implantation of autologous adult stem cells in the second surgical time. Bone union was achieved at 12 weeks. Conclusions: Within the therapeutic variants of the segmental bone defects, the membrane induction technique stands out, which in combination with the use of cell therapy constitutes a promising option, taking into account that a smaller graft volume is needed, rapid consolidation, as well as an economical alternative, and easy to make without great technological complexity.

Therapeutic Strategies in the Fight against COVID-19: From Bench to Bedside.

In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China. This virus rapidly spread worldwide and was declared a global pandemic by the World Health Organization (WHO) in March 2020. High incidence, long incubation period, and diverse clinical signs of the disease posed a huge challenge globally. The efforts of health systems have been focused on repurposing existing drugs or developing innovative therapies to reduce the morbidity and mortality associated with SARS-CoV-2. In addition, most of the large pharmaceutical companies are intensely working on vaccine development to swiftly deliver safe and effective vaccines to prevent further spread of the virus. In this review, we will discuss the latest data on therapeutic strategies undergoing clinical trials. Additionally, we will provide a summary of vaccines currently under development.

Localized Perivascular Therapeutic Approaches to Inhibit Venous Neointimal Hyperplasia in Arteriovenous Fistula Access for Hemodialysis Use.

An arteriovenous fistula (AVF) is the preferred vascular access for chronic hemodialysis, but high failure rates restrict its use. Optimizing patients' perioperative status and the surgical technique, among other methods for preventing primary AVF failure, continue to fall short in lowering failure rates in clinical practice. One of the predominant causes of AVF failure is neointimal hyperplasia (NIH), a process that results from the synergistic effects of inflammation, hypoxia, and hemodynamic shear stress on vascular tissue. Although several systemic therapies have aimed at suppressing NIH, none has shown a clear benefit towards this goal. Localized therapeutic approaches may improve rates of AVF maturation by providing direct structural and functional support to the maturating fistula, as well as by delivering higher doses of pharmacologic agents while avoiding the adverse effects associated with systemic administration of therapeutic agents. Novel materials-such as polymeric scaffolds and nanoparticles-have enabled the development of different perivascular therapies, such as supportive mechanical devices, targeted drug delivery, and cell-based therapeutics. In this review, we summarize various perivascular therapeutic approaches, available data on their effectiveness, and the outlook for localized therapies targeting NIH in the setting of AVF for hemodialysis use. Highlights: Most systemic therapies do not improve AVF patency outcomes; therefore, localized therapeutic approaches may be beneficial. Locally delivered drugs and medical devices may improve AVF patency outcomes by providing biological and mechanical support. Cell-based therapies have shown promise in suppressing NIH by delivering a more extensive array of bioactive substances in response to the biochemical changes in the AVF microenvironment.

Regulatory and clinical development to support the approval of advanced therapies medicinal products in Japan.

INTRODUCTION: A new category of products, i.e. regenerative medicine products (RPs), has been defined for advanced therapies medicinal products in Japan, as well as a legislative and regulatory framework to promote their clinical development. AREAS COVERED: This review analyses the most relevant features of the regulatory strategies and clinical development that led RPs to their approval in Japan. EXPERT OPINION: As of 31st September 2021, a total of 14 RPs were approved for 16 indications. From a regulatory standpoint, the available designations allow attractive benefit packages that promote the development of innovative products in Japan and is one of the key points to consider when the global regulatory strategy for the product is being developed. RPs regulations in Japan allow adaptive licensing and constitute shortcut through the clinical development to the approval. RPs have been mainly approved so far based on small studies with inconclusive and limited evidence of efficacy and safety, prioritizing the unmet medical needs of the target diseases, and therefore, the early access for patients. This review also compares the regulatory and clinical development for the current approved RPs in Japan with the development trends in the European Union and United States of America.

Bioengineering Human Tissues and the Future of Vascular Replacement.

Cardiovascular defects, injuries, and degenerative diseases often require surgical intervention and the use of implantable replacement material and conduits. Traditional vascular grafts made of synthetic polymers, animal and cadaveric tissues, or autologous vasculature have been utilized for almost a century with well-characterized outcomes, leaving areas of unmet need for the patients in terms of durability and long-term patency, susceptibility to infection, immunogenicity associated with the risk of rejection, and inflammation and mechanical failure. Research to address these limitations is exploring avenues as diverse as gene therapy, cell therapy, cell reprogramming, and bioengineering of human tissue and replacement organs. Tissue-engineered vascular conduits, either with viable autologous cells or decellularized, are the forefront of technology in cardiovascular reconstruction and offer many benefits over traditional graft materials, particularly in the potential for the implanted material to be adopted and remodeled into host tissue and thus offer safer, more durable performance. This review discusses the key advances and future directions in the field of surgical vascular repair, replacement, and reconstruction, with a focus on the challenges and expected benefits of bioengineering human tissues and blood vessels.

Aplicación de células madres autólogas en pacientes con aterosclerosis obliterante grado IV / Application of autologous stem cells in patients with grade IV atherosclerosis obliterans

RESUMEN Introducción: la enfermedad arterial periférica de los miembros inferiores afecta a un elevado porcentaje de la población mundial, con las células madres autólogas obtenidas de sangre periférica se logra una mayor síntesis de factores de crecimiento que inducen la angiogénesis. Objetivo: describir el autotrasplante de células madres autólogas obtenidas de sangre periférica en pacientes con aterosclerosis obliterante grado IV, de Pinar del Río, atendidos en el período de 2009-2019. Métodos: se realizó un estudio descriptivo, longitudinal, con 296 pacientes que presentaban aterosclerosis obliterante grado IV durante en el período de 2009-2019. Se obtuvo el concentrado de células madres autólogas de sangre periférica. Las células se analizaron por citometría de flujo, donde mostraron una viabilidad celular del 99,3 %. Se les inyectó por vía intramuscular un concentrado de células madres con un número de células inyectadas de ocho, seis, diez. Las variables estudiadas fueron: índice de presión tobillo-brazo en reposo, distancia de claudicación libre de dolor, evaluación de la escala del dolor y criterio de amputación. Resultado: se observó alivio del dolor a las cuatro semanas y aumento de la distancia de claudicación libre de dolor. La angiografía post tratamiento mostró formación de vasos colaterales. Presentaron criterio de amputación 95 casos (32 %) se logró salvar la extremidad en 201 pacientes (68 %). El proceder realizado no se asoció con ninguna complicación. Conclusión: la aplicación de células madres autólogas de sangre periférica es segura y eficaz para el tratamiento de la aterosclerosis obliterante grado IV.

ABSTRACT Introduction: peripheral arterial disease of the lower limbs affects a high percentage of the world population; with autologous stem cells obtained from peripheral blood a greater synthesis of growth factors that induce angiogenesis is achieved. Objective: to describe the auto-transplantation of autologous stem cells obtained from peripheral blood in patients with grade IV atherosclerosis obliterans in Pinar del Rio treated during period 2009-2019. Methods: a descriptive, longitudinal study was carried out with 296 patients with grade IV atherosclerosis obliterans during the period 2009-2019. Autologous peripheral blood stem cell concentrate was obtained. The cells were analyzed by flow cytometry, where they showed a cell viability of 99,3 %. Stem cell concentrate was injected intramuscularly with a number of cells injected of eight, six and ten. The variables studied were ankle-brachial pressure index at rest, pain-free claudication distance, pain scale assessment and amputation criteria. Result: pain relief was observed at four weeks and increase in pain-free claudication distance. Post-treatment angiography showed collateral vessel formation. Amputation criteria were met in 95 cases (32 %) and the limb was saved in 201 patients (68 %). The procedure carried out was not associated with complications. Conclusion: the application of autologous peripheral blood stem cells is safe and effective for the treatment of grade IV atherosclerosis obliterans.

Process, resource and success factors associated with chimeric antigen receptor T-cell therapy for multiple myeloma.

Background: Chimeric antigen receptor T-cell (CAR-T) therapy represents a new frontier in multiple myeloma. It is important to understand critical success factors (CSFs) that may optimize its use in this therapeutic area. Methods: We estimated the CAR-T process using time-driven activity-based costing. Information was obtained through interviews at four US oncology centers and with payer representatives, and through publicly available data. Results: The CAR-T process comprises 13 steps which take 177 days; it was estimated to include 46 professionals and ten care settings. CSFs included proactive collaboration, streamlined reimbursement and CAR-T administration in alternative settings when possible. Implementing CSFs may reduce episode time and costs by 14.4 and 13.2%, respectively. Conclusion: Our research provides a blueprint for improving efficiencies in CAR-T therapy, thereby increasing its sustainability for multiple myeloma.

Patients with multiple myeloma can now be treated with chimeric antigen receptor T-cell (CAR-T) therapy. We studied how CAR-T therapy is used for multiple myeloma. We also studied things that could help make this therapy easier for doctors to use. The CAR-T process takes 13 steps and 177 days. It begins with the choice to use the therapy and ends about 100 days after it is used. The process uses 46 different healthcare professionals and ten different locations. We found several possible changes that can improve this process. Of these changes, three stand out. First, improved teamwork between members of the care team can help them prepare for and resolve possible problems. Second, reducing insurance red tape will make it easier to provide CAR-T therapy to patients. Third, allowing use of CAR-T therapy in places other than hospitals can help more patients receive this therapy. If applied, these three things may lower the time needed to treat patients by 14.4% and may reduce costs by 13.2%.