Stem cell investigation最新文献

筛选
英文 中文
Immune reconstitution profile after allogeneic hematopoietic stem cell transplantation with post-transplant cyclophosphamide. 同种异体造血干细胞移植后环磷酰胺的免疫重建分析。
Stem cell investigation Pub Date : 2023-01-01 DOI: 10.21037/sci-2023-002
Manuel Espinoza-Gutarra, Ayman Saad, Omer Jamy
{"title":"Immune reconstitution profile after allogeneic hematopoietic stem cell transplantation with post-transplant cyclophosphamide.","authors":"Manuel Espinoza-Gutarra, Ayman Saad, Omer Jamy","doi":"10.21037/sci-2023-002","DOIUrl":"https://doi.org/10.21037/sci-2023-002","url":null,"abstract":"","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/77/0f/sci-10-2023-002.PMC10098427.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9309525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Macrophages and stem/progenitor cells interplay in adipose tissue and skeletal muscle: a review. 巨噬细胞和干细胞/祖细胞在脂肪组织和骨骼肌中的相互作用:综述。
Stem cell investigation Pub Date : 2023-01-01 DOI: 10.21037/sci-2023-009
Malgorzata Kloc, Ahmed Uosef, Henry V Ubelaker, Jacek Z Kubiak, Rafik M Ghobrial
{"title":"Macrophages and stem/progenitor cells interplay in adipose tissue and skeletal muscle: a review.","authors":"Malgorzata Kloc,&nbsp;Ahmed Uosef,&nbsp;Henry V Ubelaker,&nbsp;Jacek Z Kubiak,&nbsp;Rafik M Ghobrial","doi":"10.21037/sci-2023-009","DOIUrl":"https://doi.org/10.21037/sci-2023-009","url":null,"abstract":"<p><p>Like all immune cells, macrophages do not act autonomously but in unison with other immune cells, surrounding tissues, and the niche they occupy. Constant exchange of information between cellular and noncellular participants within a tissue allows for preserving homeostasis and defining responses in a pathologic environment. Although molecular mechanisms and pathways involved in reciprocal signaling between macrophages and other immune cells have been known for decades, much less is known about interactions between macrophages and stem/progenitor cells. Based on the time when stem cells form, there are two stem cell types: embryonic stem cells existing only in an early embryo, which are pluripotent and can differentiate into any cell type present in an adult, and somatic (adult) stem cells formed in fetus and persisting for whole adult life. Tissues and organs have their own (tissue-specific and organ-specific) adult stem cells, which serve as a reserve for tissue homeostasis and regeneration after injury. It is still uncertain whether organ- and tissue-specific stem cells are actual stem cells or just progenitor cells. The important question is how stem/progenitor cells can sculpt macrophage phenotype and functions. Even less is known if or how macrophages can shape stem/progenitor cell functions, their divisions, and fate. We describe here examples from recent studies of how stem/progenitor cells can affect macrophages and how macrophages can influence stem/progenitor cell properties, functions, and destiny.</p>","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/25/e0/sci-10-2023-009.PMC10107080.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9383834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Immunophenotypic analysis of human adipose-derived stem cells through multi-color flow cytometry. 利用多色流式细胞术分析人脂肪干细胞的免疫表型。
Stem cell investigation Pub Date : 2023-01-01 DOI: 10.21037/sci-2023-010
Paolo Giuseppe Limoli, Marcella Nebbioso
{"title":"Immunophenotypic analysis of human adipose-derived stem cells through multi-color flow cytometry.","authors":"Paolo Giuseppe Limoli,&nbsp;Marcella Nebbioso","doi":"10.21037/sci-2023-010","DOIUrl":"https://doi.org/10.21037/sci-2023-010","url":null,"abstract":"","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/92/1c/sci-10-2023-010.PMC10266955.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9654995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Primary central nervous system lymphoma: treatment access and outcomes in HIV positive patients in a minority rich cohort. 原发性中枢神经系统淋巴瘤:少数富人群中HIV阳性患者的治疗途径和结果
Stem cell investigation Pub Date : 2023-01-01 DOI: 10.21037/sci-2023-021
Hiba Narvel, Charan Vegivinti, Sindhu Vikash, Abdul Hamid Bazarbachi, Kith Pradhan, Shuai Wang, M Bakri Hammami, Nida Narvel, Shreyas Yakkali, Shehbaz Ansari, Adnan Gulam Nabi, Turab Mohammed, Ioannis Mantzaris, Marina Konopleva, Mendel Goldfinger, Kira Gritsman, Dennis Cooper, Aditi Shastri, Nishi Shah, Noah Kornblum, Amit Verma, R Alejandro Sica
{"title":"Primary central nervous system lymphoma: treatment access and outcomes in HIV positive patients in a minority rich cohort.","authors":"Hiba Narvel,&nbsp;Charan Vegivinti,&nbsp;Sindhu Vikash,&nbsp;Abdul Hamid Bazarbachi,&nbsp;Kith Pradhan,&nbsp;Shuai Wang,&nbsp;M Bakri Hammami,&nbsp;Nida Narvel,&nbsp;Shreyas Yakkali,&nbsp;Shehbaz Ansari,&nbsp;Adnan Gulam Nabi,&nbsp;Turab Mohammed,&nbsp;Ioannis Mantzaris,&nbsp;Marina Konopleva,&nbsp;Mendel Goldfinger,&nbsp;Kira Gritsman,&nbsp;Dennis Cooper,&nbsp;Aditi Shastri,&nbsp;Nishi Shah,&nbsp;Noah Kornblum,&nbsp;Amit Verma,&nbsp;R Alejandro Sica","doi":"10.21037/sci-2023-021","DOIUrl":"https://doi.org/10.21037/sci-2023-021","url":null,"abstract":"","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/01/71/sci-10-2023-021.PMC10468403.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10524593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Current status and prospects of regenerative medicine for spinal cord injury using human induced pluripotent stem cells: a review. 利用人诱导多能干细胞治疗脊髓损伤的研究现状及展望
Stem cell investigation Pub Date : 2023-01-01 DOI: 10.21037/sci-2022-037
Mitsuhiro Inoue, Ryo Yamaguchi, Ching Chi Jimmy He, Atsushi Ikeda, Hideyuki Okano, Jun Kohyama
{"title":"Current status and prospects of regenerative medicine for spinal cord injury using human induced pluripotent stem cells: a review.","authors":"Mitsuhiro Inoue,&nbsp;Ryo Yamaguchi,&nbsp;Ching Chi Jimmy He,&nbsp;Atsushi Ikeda,&nbsp;Hideyuki Okano,&nbsp;Jun Kohyama","doi":"10.21037/sci-2022-037","DOIUrl":"https://doi.org/10.21037/sci-2022-037","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is damage to the spinal cord due to trauma or health conditions, resulting in lesions in the spinal cord. Currently, available treatment includes surgical intervention to decompress or stabilize a dislocated loose spine, steroid drugs to reduce inflammation, and subsequent rehabilitation. As there is a rising number of SCI globally, radical treatments to recover spinal cord functions have become highly anticipated. The development of new treatments is indeed progressing. Various therapeutic drug candidates are being developed in clinical trials, including neuroprotective/neurotrophic factors, antibodies for repulsive guidance molecules, and cell transplantation. Among them, with advances in stem cell biology, cell transplantation therapy is currently a promising therapeutic development for SCI. In particular, there have been various reports regarding the realization of regenerative medicine using human induced pluripotent stem cells (iPSCs). This review will introduce the advantages of cell-based therapy based on iPSC-derived neural stem/progenitor cells (iPSC-NS/PCs) and some of their mechanisms of action for functional improvement, which have recently been elucidated. Potential challenges and methodologies to realize the clinical application of iPSC-NS/PCs not only for the subacute phase but also for the chronic phase of SCI will be presented. Finally, we also introduce recent research with a view to the clinical application of spinal cord regenerative therapy and discuss future prospects.</p>","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/11/19/sci-10-2022-037.PMC10036917.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9192478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Neurogenic marker expression in differentiating human adipose derived adult mesenchymal stem cells. 分化人脂肪来源的成体间充质干细胞中的神经源性标志物表达。
Stem cell investigation Pub Date : 2023-01-01 DOI: 10.21037/sci-2022-015
Neus Gomila Pelegri, Bruce K Milthorpe, Catherine A Gorrie, Jerran Santos
{"title":"Neurogenic marker expression in differentiating human adipose derived adult mesenchymal stem cells.","authors":"Neus Gomila Pelegri,&nbsp;Bruce K Milthorpe,&nbsp;Catherine A Gorrie,&nbsp;Jerran Santos","doi":"10.21037/sci-2022-015","DOIUrl":"https://doi.org/10.21037/sci-2022-015","url":null,"abstract":"<p><strong>Background: </strong>Adipose-derived stem cells (ADSCs) are increasingly utilised in the field of neural regeneration due to their high accessibility and capacity for differentiation into neural like cells. Culturing ADSCs in the presence of various growth factors, small molecules and combinations thereof have shown promise in this regard; however, these protocols are generally complex, time-consuming and costly. The need for commercially available and chemically defined growth media/supplements is required to facilitate further developments in this area.</p><p><strong>Methods: </strong>In this study, we have examined the neural differentiation and proliferation potential of the commercially available supplements B27, CultureOne (C1) and N2 on human ADSCs (hADSCs). Through a combination of immunocytochemistry, cytokine analysis, and CNPase enzymatic assays, we provide novel insight into the neural differentiation effects of B27, C1 and N2 on hADSCs.</p><p><strong>Results: </strong>The study found that C1 and N2 supplements initiated neural differentiation of the cells, with C1 pushing differentiation towards an oligodendrocytic lineage and N2 initiating neuronal differentiation. This suggests that C1 and N2 supplements can be used to drive neural differentiation in hADSCs. However, B27 did not show significant differentiation in the time frame in which the experiments took place and therefore is unsuitable for this purpose.</p><p><strong>Conclusions: </strong>These findings highlight the utility of commercially available supplements in the neural differentiation of ADSCs and may assist in establishing simpler, more affordable differentiation protocols.</p>","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4d/3c/sci-10-2022-015.PMC10076228.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9272299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Recreating heterogeneity of bladder cancer microenvironment to study its recurrences and progression. 重建膀胱癌微环境的异质性,研究其复发和进展。
Stem cell investigation Pub Date : 2023-01-01 DOI: 10.21037/sci-2023-004
François Bordeleau, David Brownell, Stephane Chabaud, Marc-Etienne Huot, Stephane Bolduc
{"title":"Recreating heterogeneity of bladder cancer microenvironment to study its recurrences and progression.","authors":"François Bordeleau,&nbsp;David Brownell,&nbsp;Stephane Chabaud,&nbsp;Marc-Etienne Huot,&nbsp;Stephane Bolduc","doi":"10.21037/sci-2023-004","DOIUrl":"https://doi.org/10.21037/sci-2023-004","url":null,"abstract":"forms are treated by a radical cystectomy, which consists in removing the entire bladder but sometimes also the surrounding tissues (6). It should be noted that recurrences after treatment will occur in 80% of non-invasive BCa cases, which can then progress to an invasive form in 30% of patients (7). In the last three decades, no significant improvement resulted from research to reduce the mortality of the BCa. Immunotherapy has recently raised hopes, but the results still seem limited, even if they may in the future","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c0/5e/sci-10-2023-004.PMC9995704.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9470046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Femur bone marrow from brain death deceased donors as source of human mesenchymal stromal cells for cell therapy. 脑死亡死者供者股骨骨髓作为细胞治疗的人间充质基质细胞来源。
Stem cell investigation Pub Date : 2023-01-01 DOI: 10.21037/sci-2023-003
Lourdes Echarte, Alexandra Sujanov, Daniel Machin, Natalia Marquisá, Cristina Touriño
{"title":"Femur bone marrow from brain death deceased donors as source of human mesenchymal stromal cells for cell therapy.","authors":"Lourdes Echarte,&nbsp;Alexandra Sujanov,&nbsp;Daniel Machin,&nbsp;Natalia Marquisá,&nbsp;Cristina Touriño","doi":"10.21037/sci-2023-003","DOIUrl":"https://doi.org/10.21037/sci-2023-003","url":null,"abstract":"<p><strong>Background: </strong>The use of a deceased donor (DD) as an alternative source of human mesenchymal stromal cells (hMSC) is promising, but has been little explored. This study evaluated the potential of femur bone marrow (FBM) from brain-death donors as a source of hMSC and compared this with hMSC from matched iliac crest bone marrow (ICBM).</p><p><strong>Methods: </strong>Sixteen donor-matched FBM and ICBM samples were processed from brain-death donors. We analyzed the starting material and compared cell yield, phenotypic profile and differentiation capacity of hMSC.</p><p><strong>Results: </strong>Neither the amount of nucleated cells per gram (14.6×10<sup>6</sup>±10.3×10<sup>6</sup> from FBM <i>vs.</i> 38.8×10<sup>6</sup>±34.6×10<sup>6</sup> from ICBM, P≥0.09) nor the frequency of CFU-F (0.0042%±0.0036% in FBM <i>vs.</i> 0.0057%±0.0042% in ICBM, P≥0.73) differ significantly from FBM or ICBM. Cell cultures from both sources were obtained and hMSC yields showed that there were no significant differences in hMSC obtained per gram of bone marrow (BM) when comparing femur with iliac crest samples. At passage 2, 12.5×10<sup>6</sup>±12.9×10<sup>6</sup> and 5.0×10<sup>6</sup>±4.4×10<sup>6</sup> hMSC per gram of BM were obtained from FBM and ICBM, respectively. FBM and ICBM hMSC express CD73, CD90, CD105, but not hematopoietic lineage markers [CD45, CD34, CD11, CD19 and isotype of HLA clase II (HLA-DR)]. HLA-A expression from both sources was clearly detected, while HLA-B was weakly expressed or undetectable and HLA-DR was undetectable. Cells from both sources were differentiated <i>in vitro</i> into osteoblasts, adipocytes and chondroblasts.</p><p><strong>Conclusions: </strong>To our knowledge, there are no previous studies evaluating BM from femur dead donors as a source of hMSC. Our findings confirm that it is feasible to expand cells from FBM from brain-death donors meeting <i>in vitro</i> characteristics of hMSC, making them a promising source for clinical translation.</p>","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ec/49/sci-10-2023-003.PMC10248827.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9619552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Adverse events, side effects and complications in mesenchymal stromal cell-based therapies. 间充质基质细胞治疗的不良事件、副作用和并发症。
Stem cell investigation Pub Date : 2022-11-08 eCollection Date: 2022-01-01 DOI: 10.21037/sci-2022-025
Denis S Baranovskii, Ilya D Klabukov, Nadezhda V Arguchinskaya, Anna O Yakimova, Anastas A Kisel, Elena M Yatsenko, Sergei A Ivanov, Peter V Shegay, Andrey D Kaprin
{"title":"Adverse events, side effects and complications in mesenchymal stromal cell-based therapies.","authors":"Denis S Baranovskii,&nbsp;Ilya D Klabukov,&nbsp;Nadezhda V Arguchinskaya,&nbsp;Anna O Yakimova,&nbsp;Anastas A Kisel,&nbsp;Elena M Yatsenko,&nbsp;Sergei A Ivanov,&nbsp;Peter V Shegay,&nbsp;Andrey D Kaprin","doi":"10.21037/sci-2022-025","DOIUrl":"https://doi.org/10.21037/sci-2022-025","url":null,"abstract":"<p><p>Numerous clinical studies have shown a wide clinical potential of mesenchymal stromal cells (MSCs) application. However, recent experience has accumulated numerous reports of adverse events and side effects associated with MSCs therapy. Furthermore, the strategies and methods of MSCs therapy did not change significantly in recent decades despite the clinical impact and awareness of potential complications. An extended understanding of limitations could lead to a wider clinical implementation of safe cell therapies and avoid harmful approaches. Therefore, our objective was to summarize the possible negative effects observed during MSCs-based therapies. We were also aimed to discuss the risks caused by weaknesses in cell processing, including isolation, culturing, and storage. Cell processing and cell culture could dramatically influence cell population profile, change protein expression and cell differentiation paving the way for future negative effects. Long-term cell culture led to accumulation of chromosomal abnormalities. Overdosed antibiotics in culture media enhanced the risk of mycoplasma contamination. Clinical trials reported thromboembolism and fibrosis as the most common adverse events of MSCs therapy. Their delayed manifestation generally depends on the patient's individual phenotype and requires specific awareness during the clinical trials with obligatory inclusion in the patient' informed consents. Finally we prepared the safety checklist, recommended for clinical specialists before administration or planning of MSCs therapy.</p>","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/95/a8/sci-09-2022-025.PMC9659480.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40482408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 32
An autologous humanized patient-derived xenograft (PDX) model for evaluation of nivolumab immunotherapy in renal cell cancer: a case report. 用于评估肾细胞癌 nivolumab 免疫疗法的自体人源化患者异种移植 (PDX) 模型:病例报告。
Stem cell investigation Pub Date : 2022-11-08 eCollection Date: 2022-01-01 DOI: 10.21037/sci-2022-029
Yubin Kang, Andrew J Armstrong, David S Hsu
{"title":"An autologous humanized patient-derived xenograft (PDX) model for evaluation of nivolumab immunotherapy in renal cell cancer: a case report.","authors":"Yubin Kang, Andrew J Armstrong, David S Hsu","doi":"10.21037/sci-2022-029","DOIUrl":"10.21037/sci-2022-029","url":null,"abstract":"<p><strong>Background: </strong>There is an unmet need for developing faithful animal models for preclinical evaluation of immunotherapy. The current approach to generate preclinical models for immunotherapy evaluation has been to transplant CD34<sup>+</sup> cells from umbilical cord blood into immune-deficient mice followed by implantation of patient derived tumor cells. However, current models are associated with high tumor rejection rate secondary to the allograft <i>vs.</i> tumor response from human leukocyte antigen (HLA) mismatches. We herein report the first development of a novel, humanized patient-derived xenograft (PDX) model using autologous CD34<sup>+</sup> cells from bone marrow aspirate obtained from a patient with metastatic clear cell renal cell carcinoma (mRCC) from whom a PDX had been developed.</p><p><strong>Case description: </strong>This is a 68-year-old Caucasian man diagnosed with mRCC with metastasis to the liver in 2014. He was treated with sunitinib +/- AGS-003 and underwent a cytoreductive right nephrectomy, left adrenalectomy and partial liver resection. PDX was generated using resected nephrectomy specimen. After surgery, patient received multiple lines of standard of care therapy including sunitinib, axitinib, bevacizumab, everolimus and cabozantinib. While progressing on cabozantinib, he was treated with nivolumab. Seven years after initiation of nivolumab, and 4 years after stopping systemic therapy, he remains in complete remission. To generate autologous PDX model, bone marrow aspirate was performed and CD34<sup>+</sup> hematopoietic stem/progenitor cells (HSPCs) were isolated and injected into 150 rad irradiated non-obese diabetic scid gamma null (NSG) mice. At 11 weeks post-transplant, the matched patient PDX was injected subcutaneously into the humanized mice and the mice were treated with nivolumab.</p><p><strong>Conclusions: </strong>Our case represents successful therapy of nivolumab in mRCC. Furthermore, HPSCs obtained from a single bone marrow aspirate were able to reconstitute an immune system in the mice that allowed nivolumab to inhibit the tumor growth of PDX and recapitulated the durable remission observed in the patient with nivolumab. We observed the reconstitution of human T cells, B cells and natural killer (NK) cells and unlike the humanized mouse model using cord blood, our model system eliminates the tumor rejection from mis-matched HLA. Our autologous humanized renal cell carcinoma (RCC) PDX model provides an effective tool to study immunotherapy in a preclinical setting.</p>","PeriodicalId":21938,"journal":{"name":"Stem cell investigation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bd/59/sci-09-2022-029.PMC9659479.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9650449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信