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2.
Stem Cell Reports ; 16(11): 2567-2576, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1525954

ABSTRACT

The significant morbidity and mortality of coronavirus disease 19 (COVID-19) prompted a global race to develop new therapies. These include interventions using cell- or cell-derived products, several of which are being tested in well-designed, properly controlled clinical trials. Yet, the search for cell-based COVID-19 treatments has also been fraught with hyperbolic claims; flouting of crucial regulatory, scientific, and ethical norms; and distorted communication of research findings. In this paper, we critically examine ethical issues and public communication challenges related to the development of cell-based therapeutics for COVID-19. Drawing on the lessons learned from this ongoing process, we argue against the rushed development of cell-based interventions. We conclude by outlining ways to improve the ethical conduct of cell-based clinical investigations and public communication of therapeutic claims.


Subject(s)
COVID-19/therapy , Communication , Pandemics/ethics , SARS-CoV-2 , Stem Cell Transplantation/ethics , Therapeutics/ethics , Humans
5.
Cells ; 10(10)2021 09 24.
Article in English | MEDLINE | ID: covidwho-1438525

ABSTRACT

The objective of this review is to describe the evolution of lung tissue-derived diploid progenitor cell applications, ranging from historical biotechnological substrate functions for vaccine production and testing to current investigations around potential therapeutic use in respiratory tract regenerative medicine. Such cell types (e.g., MRC-5 or WI-38 sources) were extensively studied since the 1960s and have been continuously used over five decades as safe and sustainable industrial vaccine substrates. Recent research and development efforts around diploid progenitor lung cells (e.g., FE002-Lu or Walvax-2 sources) consist in qualification for potential use as optimal and renewed vaccine production substrates and, alternatively, for potential therapeutic applications in respiratory tract regenerative medicine. Potentially effective, safe, and sustainable cell therapy approaches for the management of inflammatory lung diseases or affections and related symptoms (e.g., COVID-19 patients and burn patient severe inhalation syndrome) using local homologous allogeneic cell-based or cell-derived product administrations are considered. Overall, lung tissue-derived progenitor cells isolated and produced under good manufacturing practices (GMP) may be used with high versatility. They can either act as key industrial platforms optimally conforming to specific pharmacopoeial requirements or as active pharmaceutical ingredients (API) for potentially effective promotion of lung tissue repair or regeneration.


Subject(s)
Biotechnology/methods , Diploidy , Lung/cytology , Regenerative Medicine/methods , Respiratory Tract Infections/therapy , Animals , Biological Specimen Banks , COVID-19 Vaccines , Cell Line , Cell- and Tissue-Based Therapy , History, 20th Century , History, 21st Century , Humans , Lung/physiology , Regeneration , Regenerative Medicine/history , SARS-CoV-2 , Stem Cell Transplantation , Stem Cells/cytology , Transplantation, Homologous
8.
Biomed Res Int ; 2021: 9915927, 2021.
Article in English | MEDLINE | ID: covidwho-1376538

ABSTRACT

Background: The SARS-CoV-2 virus is the cause of the latest pandemic of the 21st century; it is responsible for the development of COVID-19. Within the multiple study models for both the biology and the treatment of SARS-CoV-2, the use of stem cells has been proposed because of their ability to increase the immune response and to repair tissue. Therefore, the objective of this review is to evaluate the role of stem cells against SARS-CoV-2 and COVID-19 in order to identify their potential as a study model and as a possible therapeutic source against tissue damage caused by this virus. Therefore, the following research question was established: What is the role of stem cells in the study of SARS-CoV-2 and the treatment of COVID-19? Materials and Methods: A search was carried out in the electronic databases of PUBMED, Scopus, and ScienceDirect. The following keywords were used: "SARS-CoV-2," "COVID-19," and "STEM CELL," plus independent search strategies with the Boolean operators "OR" and "AND." The identified reports were those whose main objective was the study of stem cells in relation to SARS-CoV-2 or COVID-19. For the development of this study, the following inclusion criteria were taken into account: studies whose main objective was the study of stem cells in relation to SARS-CoV-2 or COVID-19 and clinical case studies, case reports, clinical trials, pilot studies, in vitro, or in vivo studies. For assessment of the risk of bias for in vitro studies, the SciRAP tool was used. The data collected for each type of study, clinical or in vitro, were analyzed with descriptive statistics using the SPSS V.22 program. Results: Of the total of studies included (n = 39), 22 corresponded to in vitro investigations and 17 to human studies (clinical cases (n = 9), case series (n = 2), pilot clinical trials (n = 5), clinical trials (n = 1)). In vitro studies that induced pluripotent stem cells were the most used (n = 12), and in clinical studies, the umbilical stem cells derived were the most reported (n = 11). The mean age of the study subjects was 58.3 years. After the application of stem cell therapy, the follow-up period was 8 days minimum and 90 days maximum. Discussion. The mechanism by which the virus enters the cell is through protein "S," located on the surface of the membrane, by recognizing the ACE2 receptor located on the target cell. The evidence that the expression of ACE2 and TMPRSS2 in stem cells indicates that stem cells from bone marrow and amniotic fluid have very little expression. This shows that stem cell has a low risk of infection with SARS-CoV-2. Conclusion: The use of stem cells is a highly relevant therapeutic option. It has been shown in both in vitro studies and clinical trials that it counteracts the excessive secretion of cytokines. There are even more studies that focus on long-term follow-up; thus, the potential for major side effects can be analyzed more clearly. Finally, the ethical use of stem cells from fetal or infant origin needs to be regulated. The study was registered in PROSPERO (no. CRD42021229038). The limitations of the study were because of the methodology employed, the sample was not very large, and the follow-up period of the clinical studies was relatively short.


Subject(s)
COVID-19/pathology , COVID-19/therapy , SARS-CoV-2/isolation & purification , Stem Cell Transplantation/methods , Stem Cells/cytology , COVID-19/metabolism , COVID-19/virology , Clinical Trials as Topic , Humans , Stem Cells/pathology
9.
Future Oncol ; 17(33): 4511-4525, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1367736

ABSTRACT

Aim: To understand the economic burden of relapsed and refractory large B-cell lymphoma patients in Japan treated with salvage chemotherapy. Patients & methods: Patients who received systemic therapy after first-line treatment were analyzed to assess its associated cost and resource use using a retrospective claims database. The impact of COVID-19 was assessed separately. Results & conclusion: This study identified 2927 and 1085 patients in the second- (2L) and third-line (3L) cohorts. The median ages for the 2L and 3L cohorts were 71 and 70 years, respectively, with Charlson Comorbidity Score of 3. A majority of the patients had limited stem cell transplant due to advanced age. Median lengths of inpatient stay for the 2L and 3L cohorts were 118 and 116 days, respectively. The majority of costs were attributed to inpatient costs, and limited COVID-19 impact was observed in this study.


Subject(s)
COVID-19/prevention & control , Cost of Illness , Lymphoma, Large B-Cell, Diffuse/economics , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/economics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , COVID-19/epidemiology , COVID-19/transmission , Communicable Disease Control/standards , Female , Humans , Japan/epidemiology , Length of Stay/economics , Length of Stay/statistics & numerical data , Lymphoma, Large B-Cell, Diffuse/epidemiology , Lymphoma, Large B-Cell, Diffuse/therapy , Male , Middle Aged , Patient Acceptance of Health Care/statistics & numerical data , Retrospective Studies , Salvage Therapy/economics , Salvage Therapy/methods , Stem Cell Transplantation/economics , Stem Cell Transplantation/statistics & numerical data
10.
Natl Med J India ; 34(1): 10-14, 2021.
Article in English | MEDLINE | ID: covidwho-1359327

ABSTRACT

Background: . Coronavirus disease 2019 (Covid-19) was first described in December 2019 and has evolved into an ongoing global pandemic. Cancer patients on chemotherapy are immunocompromised and are at the highest risk of Covid-19-related complications. We describe our experience with the management of haematology-oncology and stem cell transplant (SCT) patients receiving curative chemotherapy in a hospital with a high influx of Covid-19 patients. Methods: . We did a prospective observational study at a 99-bedded cancer centre of a tertiary care teaching hospital from April 2020 to September 2020. Preventive measures taken were categorized as follows: (i) staff: screening, mandatory use of personal protective equipment (PPE), risk stratification of potential exposure and testing and isolation as needed; (ii) patients: mandatory viral polymerase chain reaction testing, segregation of positive and untested patients and testing of family members; and (iii) environment: mandatory regular cleaning, visitor restriction, telemedicine services and reassignment of priority to clinic visits. Treatment of the underlying conditions was continued with added precautions. Results: . A total of 54 patients were included in the analysis, including 48 with haematological malignancies and 6 for stem cell therapy. Preventive measures were universally applied, and chemotherapy with a curative intent was initiated as per protocol. Three patients were detected to have Covid-19 infection before admission and one after the institution of chemotherapy. Nine patients died after the first cycle of chemotherapy, 2 due to severe Covid-19-related illness and 7 due to complications of chemotherapy or disease progression. Conclusions: . In the wake of the Covid-19 pandemic, treatment for haematological malignancies must continue while balancing the risk of Covid-19 infections. Our report emphasizes the effectiveness of measures such as hand hygiene, social isolation, patient segregation, use of masks and PPE and universal pre-treatment testing for Covid-19 in reducing the risk of infection in a high-risk clinical setting.


Subject(s)
COVID-19 , Hematologic Neoplasms , Infection Control , Risk Management , Stem Cell Transplantation , Telemedicine/organization & administration , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Testing/methods , Contact Tracing/methods , Female , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/therapy , Humans , Immunocompromised Host/immunology , India/epidemiology , Infection Control/instrumentation , Infection Control/methods , Infection Control/organization & administration , Male , Middle Aged , Prospective Studies , Risk Management/methods , Risk Management/organization & administration , SARS-CoV-2 , Stem Cell Transplantation/methods , Stem Cell Transplantation/statistics & numerical data
11.
Ann R Coll Surg Engl ; 103(7): 463, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1320542
12.
J Cereb Blood Flow Metab ; 41(10): 2797-2799, 2021 10.
Article in English | MEDLINE | ID: covidwho-1288495

ABSTRACT

The last 50 years have witnessed the translation of stem cell therapy from the laboratory to the clinic for treating brain disorders, in particular stroke. From the focal stereotaxic transplantation to the minimally invasive intravenous and intraarterial delivery, stem cells display the ability to replenish injured cells and to secrete therapeutic molecules, altogether promoting brain repair. The increased stroke incidence in COVID-19 survivors poses as a new disease indication for cell therapy, owing in part to the cells' robust anti-inflammatory properties. Optimization of the cell transplant regimen will ensure the safe and effective clinical application of cell therapy in stroke and relevant neurological disorders.


Subject(s)
COVID-19/complications , Stem Cell Transplantation , Stroke/etiology , Stroke/therapy , Animals , Brain/pathology , COVID-19/diagnosis , Humans , Incidence , Regenerative Medicine/methods , SARS-CoV-2/isolation & purification , Stem Cell Transplantation/methods , Stroke/pathology
13.
Curr Opin Pharmacol ; 59: 85-94, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275237

ABSTRACT

There is an urgent need for better treatment of lung diseases that are a major cause of morbidity and mortality worldwide. This urgency is illustrated by the current COVID-19 health crisis. Moderate-to-extensive lung injury characterizes several lung diseases, and not only therapies that reduce such lung injury are needed but also those that regenerate lung tissue and repair existing lung injury. At present, such therapies are not available, but as a result of a rapid increase in our understanding of lung development and repair, lung regenerative therapies are on the horizon. Here, we discuss existing targets for treatment, as well as novel strategies for development of pharmacological and cell therapy-based regenerative treatment for a variety of lung diseases and clinical studies. We discuss how both patient-relevant in vitro disease models using innovative culture techniques and other advanced new technologies aid in the development of pulmonary regenerative medicine.


Subject(s)
Lung Diseases/therapy , Lung/physiology , Regeneration , Animals , Humans , Stem Cell Transplantation , Stem Cells
14.
Regen Med ; 16(6): 525-533, 2021 06.
Article in English | MEDLINE | ID: covidwho-1266635

ABSTRACT

Aim: There is a critical need for safe and effective treatments for COVID-19. One possible type of treatment is cellular medicine such as stem cell therapy, but its potential is unclear. Here, our aim was to assess the potential impact of the many cellular medicine trials for COVID-19. Materials & methods: We collected and analyzed data for defined criteria from trial registries. Results: Our data suggest that relatively few of these COVID-19 trials will produce high-level evidence, but that on average they may be somewhat more rigorous than typical cell therapy trials unrelated to COVID-19. Conclusion: Most COVID-19 cellular medicine trials have relatively low potential for rapid, concrete impact. We discuss the findings in the context of the cellular medicine field overall.


Subject(s)
COVID-19 , SARS-CoV-2 , Stem Cell Transplantation , Stem Cells , Clinical Trials as Topic , Humans
15.
Clin J Oncol Nurs ; 25(3): 329-332, 2021 Jun 01.
Article in English | MEDLINE | ID: covidwho-1259220

ABSTRACT

Patients in the hematology-oncology and stem cell transplantation (SCT) setting are at high risk for functional decline and falls related to prolonged hospitalizations and inactivity during inpatient treatment. After underperforming on the Press Ganey National Database of Nursing Quality Indicators benchmark for falls in 2018, staff on a hematology-oncology and SCT unit implemented a practical and evidence-based fall prevention program. Fall rates from 2018 to 2019 ranged from 3.4 to 4.8 falls per 1,000 patient days. After the introduction of the unit-based gym program, early mobility increased and falls decreased to 2.57 per 1,000 patient days.


Subject(s)
Hematology , Inpatients , Humans , Stem Cell Transplantation
16.
HNO ; 69(8): 623-632, 2021 Aug.
Article in German | MEDLINE | ID: covidwho-1227814

ABSTRACT

Olfactory disorders may be temporary or permanent and can have various causes. Currently, many COVID-19 patients report a reduced or complete loss of olfactory function. A wide range of treatment options have been investigated in the past, such as olfactory training, acupuncture, medical therapy, transcranial magnetic stimulation, or surgical excision of olfactory epithelium, e.g., in severe qualitative smell disorders. The development of a bioelectric nose, e.g., in connection with direct electrical stimulation or transplantation of olfactory epithelium or stem cells, represent treatment options of the future. The basis of these developments and the state of knowledge is discussed in the following work.


Subject(s)
COVID-19 , Olfaction Disorders , Electric Stimulation , Humans , Olfactory Mucosa , SARS-CoV-2 , Smell , Stem Cell Transplantation
18.
Bone Marrow Transplant ; 56(9): 2272-2275, 2021 09.
Article in English | MEDLINE | ID: covidwho-1193585

ABSTRACT

The Transplant Centers belonging to Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO) conducted a survey with the aim of evaluating the effect of SARS-CoV2 pandemic on the allogeneic transplant activity in Italy. The pandemic period from 1/3/2020 to 31/7/2020 was compared with the same period in 2019. Overall, in 2020 there was a 2.4% reduction in the number of allo-HCT cases compared to 2019. Interestingly, this deflection did not affect the acute leukemia cases (+5.7% in 2020). The use of peripheral blood-derived stem cells (+10.7%) and cryopreservation (97.4% of the centers) was highly adopted in 2020. Despite the sanitary emergency, almost all of the surveyed centers declared no impact of SARS-CoV2 pandemic on the transplant timing and outcomes, and the sanitary policy was positively evaluated by the majority of centers. The emergency measures ensured that only a minority of the allo-HCT patients had been infected by SARS-CoV2; however, a mortality of 42.1% among the allo-HCT patients hospitalized for COVID-19 was recorded. This survey gives us the information that the GITMO Group reacted positively to the pandemic. Thanks to the emergency strategies, the Italian allo-HCT activity continued safely, showing only a minor deflection and offering the same probability of cure to the transplanted patients.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Humans , Italy/epidemiology , Pandemics , RNA, Viral , SARS-CoV-2 , Stem Cell Transplantation , Transplantation, Homologous
19.
Front Endocrinol (Lausanne) ; 12: 596654, 2021.
Article in English | MEDLINE | ID: covidwho-1167312

ABSTRACT

In early 2020, a novel coronavirus leading to potentially death was discovered. Since then, the 2019 coronavirus disease (COVID-19) has spread to become a worldwide pandemic. Beyond the risks strictly related to the infection, concerns have been expressed for the endocrinological impact that COVID-19 may have, especially in vulnerable individuals with pre-existing endocrinological health conditions. To date new information is emerging regarding severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in children but the literature is still scarce concerning this infection in patients with intracranial malignant neoplasms. We report a 9-year-old child infected with SARS-CoV-2 and recent diagnosis of suprasellar non-germinomatous germ cell tumor also suffering from diabetes insipidus and hypothalamic-pituitary failure (hypothyroidism, adrenal insufficiency, hypothalamic obesity and growth hormone deficiency) and its clinical course. The patient remained asymptomatic for the duration of the infection without requiring any change in the replacement therapeutic dosages taken before the infection. We then discuss the proposed approach to treat a pediatric patient with SARS-CoV-2 infection and hypothalamic-pituitary failure and we include a review of the literature. Our report suggests that SARS-CoV-2 infection is usually mild and self-limiting in children even those immunocompromised and with multiple endocrinological deficits. Patients are advised to keep any scheduled appointments unless informed otherwise.


Subject(s)
COVID-19/complications , Hypothalamo-Hypophyseal System/physiopathology , Neoplasms, Germ Cell and Embryonal/complications , Neoplasms, Germ Cell and Embryonal/therapy , Pituitary Neoplasms/complications , Pituitary Neoplasms/therapy , COVID-19/physiopathology , COVID-19/therapy , Child , Diabetes Insipidus/complications , Diabetes Insipidus/physiopathology , Female , Humans , Magnetic Resonance Imaging , Neoplasms, Germ Cell and Embryonal/physiopathology , Pituitary Neoplasms/physiopathology , Quarantine , Stem Cell Transplantation
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