Stem cell investigation最新文献

Background: Hematopoietic stem cell transplant (HSCT) is an expensive and complex treatment regimen that can be curative in many diseases of the bone marrow, including malignant and non-malignant conditions. The introduction of the Affordable Care Act increased access to potential candidates and removed or reduced many barriers previously identified in the literature, however, racial disparities continue to persist. As HSCT expands its utilization and indications, there is a continued need to understand the multifactorial barriers which lead to inequalities in transplant referral, utilization, and survival. The objective of this systematic review is to summarize these racial disparities, expand the current understanding of the literature, and determine whether the increases in insurance status from Medicaid expansion have played a role in HSCT utilization and survival rates by race.

Methods: We explored studies based on retrospective reviews, literature reviews, and focus groups with the key-terms of 'race', 'hematopoietic stem cell transplant', and 'disparities'. The included studies were extracted from Cochrane and Medline databases. After screening for relevancy to research aims and objectives, 10 articles were utilized for background information and discussion, while 30 articles were categorized into main groups of outcomes, chiefly, (I) access/referral to transplant and (II) survival.

Results: Eight of the eleven retrospective reviews found substantial variation in access to HSCT by ethnic minorities (Black, Hispanic, or Asian) when compared to their Caucasian counterparts. Thirteen of the fourteen publications found racial disparities in either overall survival, progression free survival, treatment related mortality, relapse, or combinations of these outcomes. The majority of the studies evaluated African American patients with six of eight studies showing significantly elevated mortality compared to Caucasian patients.

Discussion: Substantial variation exists in access to HSCT, particularly in black patients. Having less generous insurance coverage was previously hypothesized to reduce the likelihood of HSCT utilization. Studies performed after full implementation of the Affordable Care Act continue to show poorer survival among ethnic minorities, particularly black patients, despite this increased coverage. Perceived racial bias and health-related stigma, as well as physician decisions and delay in referral process are likely contributing factors.

Objective: The objective of this review article is to outline the pathology, virology and mechanism of severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2) and to study the regenerative role of mesenchymal stem cells (MSCs) to tackle the lung damage caused by SARS-CoV-2.

Background: The MSCs possess trophic potentialities which enable them to find out the sites of injury or inflammation and because of their pleiotropic and pericytic nature, these cells are capable of differentiating into different cell types. The MSCs can be derived from a variety of tissue sources be it adult or embryonic origin. The one major characteristic of MSCs is that they are immunologically naïve in terms of expression of MHC Class II. This very low or no expression of MHC class II makes them useful in clinical settings where they can be used in allogenic transplant cases. This allogenic transplant possibilities of these MSCs makes them one of the most researched stem cells and investigated for cell-based therapies. Though these MSCs are in clinical settings for long the one even more important characteristic which makes them even more in demand is their immunomodulatory properties which have been used in various cases to mitigate the effect of overstimulation of the immune system. In recent times after the pandemic of the novel corona virus disease 2019 (nCOVID-19) generated by SARS-CoV-2, the effect of various MSCs isolated from various tissue sources are being utilized to curb the overstimulation of immune response, so that the immune system can be brought under some regulation to ultimately reduce the effect of inflammation.

Methods: In this review article, we have reviewed the existing literature, data and ongoing clinical trials by using keywords like novel coronavirus, COVID-19, SARS-CoV-2, MERS-CoV, acute respiratory distress syndrome, mesenchymal stem cells, immunomodulation properties of stem cells, regenerative properties of stem cells, cell therapy, clinical trials of stem cells, clinical trials of COVID-19 and stem cells till 20th August 2020 using database named PubMed, NCBI, Google Scholar, Scopus, Research Gate and Clinicaltrials.gov.

Conclusions: Thus, concluding the therapeutic potential of MSCs in managing and treating COVID-19.

Objective: To systematically review the ongoing progress of effective treatment of advanced hepatocellular carcinoma (HCC), mainly focusing on immune checkpoint inhibitors (ICPI) as monotherapy and combination therapy.

Background: HCC in general has a poor prognosis; particularly in the advanced stage. For more than 10 years, the treatment with multikinase inhibitors was the first line treatment. Before the introduction of checkpoint inhibitors, very few treatments were available for patients with hepatocellular cancer in the advanced stage, especially in metastatic and unresectable disease.

Methods: We performed an extensive search of the ongoing and published clinical trials in the English written literature concerning of HCC with immune checkpoint inhibition when compared to first line chemotherapy.

Conclusions: The treatment paradigm for advanced stage HCC has significantly changed recently with the introduction of immunotherapy; based on existing research, there is new era for HCC treatment which will positively affect the outcome in a malignancy that did not see therapy advancement for more than a decade. Monoclonal antibodies against programmed death ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1), such as nivolumab and pembrolizumab appear to be a promising therapeutic option in HCC. This review outlines immunotherapy that has been approved, and what inhibitors are under investigation for patients with advanced stage HCC.

Background: Intrinsic factors related to self-renewal regulatory factors in hematopoietic stem cells are well known; however, limited information is available on extrinsic factors, such as the cell environment. Therefore, in this study, we analyzed the regulatory mechanism of hematopoietic stem cell self-renewal, focusing on the osteoblastic niche, and examined how adherence to osteoblasts affects stem cell differentiation.

Methods: For this experimental study, we developed a co-culture system for hematopoietic stem cells and osteoblasts, such that cells adhered to osteoblasts can be separated from those that do not. Murine Sca1-positive cells were separated into groups according to whether they were attached to osteoblasts or detached from osteoblasts, and each group was then subjected to colony assays and bone marrow transplantation experiments.

Results: Adhered Sca1-positive cells developed more secondary colonies than non-adhered Sca1-positive cells. Furthermore, in bone marrow transplantation experiments, adhered Sca1-positive cells showed successful engraftment. We explored the role of Polycomb genes in the regulation of cell fate and found that self-renewing cells attached to osteoblasts had high Bmi-1 expression and low Mel-18 expression, while this expression was reversed in differentiating cells.

Conclusions: Our results suggest that hematopoietic stem cells self-renew when they remain in osteoblastic niches after cell division. Further, when stem cells leave the niches, they undergo differentiation.

Objective: Interspecific human-animal chimerism via blastocyst complementation provides a promising strategy to generate function human cells, tissues or organs from human pluripotent stem cells (hPSCs), although it is still quite challenging. In this review, we will mainly focus on the recent advances, such as the options of donor hPSCs and the understanding of interspecific chimera barriers, challenges, and perspectives on the efficient generation of human-animal interspecies chimeras.

Background: hPSCs, including the human embryonic stem cells (hESCs) and the human induced pluripotent stem cells (hiPSCs) hold great promise for regenerative medicine to treat various degenerative diseases. However, although hPSCs can differentiate to all lineage cells in dish, the functionality of these cells is limited, hinting that the in vitro differentiation system failed to fully recapture the in vivo development. A promising alternative strategy is in vivo generation of functional human cells in animals through interspecies chimerism, based on the principle that mammalian development is highly conserved across species. This strategy was inspired by the successful generation of functional rat pancreas in mice through blastocyst injection of rat pluripotent stem cells (PSCs). Over the past ten years, since this milestone work was reported, advances have been made in the human-animal interspecies chimerism. However, it is still challenging to efficiently generate human cells, tissues, or organs in the interspecies chimeras. This phenomenon suggests that there are still obstacles to illustrate and overcome implicated in human-animal interspecies chimeras.

Methods: Narrative overview of the literatures reported the recent advances, challenges and perspectives regarding the interspecies chimerism via blastocyst complementation.

Conclusions: Human-animal interspecies chimerism via blastocyst complementation is a valuable method to generate functional human cells, tissues or organs, while there are at least three barriers need to be overcome. Firstly, conventional hPSCs should be converted to possess the chimera competency; secondly, efficient human-animal chimerism are required to robustly generate human derivatives in chimera; thirdly, the discrepancy regarding the developmental regulation network between human and host animals must be eliminated to generate certain human cells, tissues or organs in the interspecies chimeras.

Background: Adoptive immunotherapy using CD19-targeted Chimeric antigen receptor T cells (CAR-T) has revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Data is limited on the propensity of infections and lymphohematopoietic reconstitution after Day 30 (D30) following CAR-T cell therapy. In this study, we evaluated the prevalence and nature of infectious complications in an expanded cohort of DLBCL patients treated with CD19 CAR-T therapy and its association with the dynamics of leukocyte subpopulation reconstitution post-CAR-T cell therapy.

Methods: We conducted a retrospective study including 19 patients who received axicabtagene ciloleucel and investigated associations between cytopenia and infectious complications after D30.

Results: Nineteen patients were included, consisting of 42% Hispanic, 32% Caucasian, 21% African-American, and 5% Asian subjects. Post-D30 of CAR-T infusion, 47% patients (n=9) developed an infection and 53% (n=10) remained infection-free. The most common infection type observed was viral (7 patients) followed by bacterial (5 patients) and fungal (3 patients). Of 25 total infectious events, 56% were grade 1 or 2 and 44% were grade 3 with 10 being viral in etiology. To determine the kinetics of lymphohematopoietic reconstitution and its association with infection risk, we evaluated the relationship between cytopenias and rates of infection after D30. Notably, compared to non-infection group, infection group had a higher median absolute lymphocyte count (ALC) (1,000/µL vs. 600/µL, P<0.05), a lower median absolute neutrophil count (ANC)/ALC ratio (1.6 vs. 3.1, P<0.05) and a lower median AMC/ALC at D30 (0.37 vs. 1.67, P<0.05). In addition, we observed that only 22% of patients had recovered ANC >1,500/µL in the infection group as opposed to 70% in the non-infection group at D90 (P<0.05). Fifty-eight percent of the patients (11/19) with relapsed refractory DLBCL achieved a complete response with a median follow-up of 233 days (7.7 months).

Conclusions: Although CAR-T cell therapy is highly effective, infectious complications remain an important cause of morbidity and mortality. Low ANC/ALC and AMC/ALC ratios at D30 are potential novel predictors of infection and can be considered in future prophylactic strategies.

The most common cancer in the United States is non-melanoma skin cancer. Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer after basal cell carcinoma. It develops in the middle and outer layers of the skin. Its precursor is actinic keratosis, which can progress to squamous cell carcinoma in situ, invasive cSCC, and finally metastatic cSCC. About 20% of non-melanoma skin cancers are squamous cell and the remaining 80% are basal cell. Unlike basal cell, squamous cell carcinoma has the propensity to metastasize. This commonly occurs with squamous cell carcinoma (SCC) thicker than 2 millimeters. The risk of metastasis and local recurrence increases with 6 mm thickness and desmoplasia. The risk factors are excessive sun or ultraviolet light (tanning beds) exposure, immunosuppression (either having a weakened immune system or taking immunosuppressive therapy) and fair skin. Therefore, it most commonly affects skin in the head and neck area such as scalp, ears, lips, face, neck or the back of the hands. The treatment for local cutaneous squamous cell cancer is mainly surgery; excisional surgery, Moh's surgery, cryosurgery, curettage and electrodessication, laser surgery or radiation therapy, photodynamic therapy or topical agents such as fluorouracil or imiquimod. However, cSCC that is locally advanced, such as involvement of regional lymph nodes, or has metastasized to distant organs or tissue, is not amenable to surgery or radiation alone. Immunotherapy with cemiplimab, a programmed cell death 1 (PD-1) inhibitor, is a US Food and Drug Administration (FDA) approved therapeutic option for locally advanced and metastatic cSCC for patients who are not candidates for or whose disease is not susceptible to curative surgery or radiation therapy. Cemiplimab is a humanized recombinant immunoglobulin monoclonal antibody that binds to and blocks PD-1 receptor found on T cells inhibiting T-cell proliferation and cytokine production. We present a case of locally advanced cSCC with regional lymph nodes metastases, which achieved clinical remission, utilizing a unique approach of therapy combining a checkpoint inhibitor, Cemiplimab and radiotherapy.

[This corrects the article DOI: 10.21037/sci-2020-021.].

Background: Stem cells from human exfoliated deciduous teeth (SHED) are regarded as an attractive cell source for tissue regeneration. However, the effect of different levels of root resorption on the characteristics of SHED remains less understood. Thus, the tooth source that is most suitable for the isolation of SHEDs needs to be determined. To compare cellular and biological characteristics of stem cells from human exfoliated deciduous posterior teeth with varying levels of root resorption.

Methods: The pulp was obtained from the deciduous posterior teeth depending on the level of root resorption, and isolated SHEDs were grouped as follows: Teeth with 0 to 1/3^rd root resorption as SHEDs (G1) and 1/3^rd to 2/3^rd root resorption as SHEDs (G2). Teeth were also collected from >2/3^rd root resorption status, but failed to establish primary culture of SHED as the availability of pulp tissue was too less. Later, isolated SHEDs were compared on their morphology, viability, growth kinetics, colony-forming ability, expression of cell surface markers and in vitro differentiation into osteocytes and adipocytes.

Results: No major differences were observed in terms of cellular morphology, viability, proliferation rate, colony-forming ability, cell surface markers expression, and mesenchymal lineage differentiation of SHEDs isolated from posterior teeth with 0 to 1/3^rd and 1/3^rd to 2/3^rd root resorption. However, SHED from teeth with 0 to 1/3^rd root resorption (G1) displayed relatively higher proliferation capacity and expression of selected markers.

Conclusions: Collectively, SHEDs (G1) and SHEDs (G2) showed comparable cellular and biological characteristics that enable their possible applications in regenerative therapies.

Management of keratocystic odontogenic tumor (KCOT) has always remained a conundrum due to its aggressive behavior, indicating wide resection. Achieving an esthetically and functionally acceptable reconstruction remains a challenge. Herein, we present a novel and less invasive technique for the treatment of KCOT. A 55-year-old female presenting with pain in the lower jaw for the past 3 months was diagnosed with a large KCOT extending from 35 to 47 region. CT images revealed buccal and lingual cortical bone erosion. Management was done in two stages: cyst curettage and chemical cauterization, followed by application of Bone Marrow Aspirate Concentrate (BMAC) with a delay of two months, to increase the thickness of eroded cortical bone. On follow-up at one year, ossification of the defect was observed. BMAC is a cocktail of mesenchymal stromal cells, hematopoietic stem cells, fibroblasts, mononuclear cells, macrophages, endothelial cells, progenitor cells, growth factors and cytokines. BMAC cocktail provide an anti-inflammatory, anti-fibrotic, anti-apoptotic, and immunomodulatory environment. Autologous platelet rich plasma provides various growth factors (TGF-β, PDGF, EGF, HGF, NGF, IGF-1) and cytokines. Addition of PRP in BMAC cocktail enhance the regeneration of tissues, where PRP act as a functional regenerative scaffold for cell integration, proliferation, and differentiation that can expedite macroscale musculoskeletal tissue healing. Autologous BMAC with corticocancellous bone acts as an osteoconductive scaffold capable of regenerating the large bone defect created by the curettage of KCOT.