Evidence from a humanized mouse model of androgenetic alopecia that platelet‐rich plasma (PRP) stimulates hair regrowth, hair shaft diameter and vellus‐to‐terminal hair reconversion in vivo

2021 ◽  
Author(s):  
R. Laufer Britva ◽  
A. Keren ◽  
A. Ginzburg ◽  
Y. Ullmann ◽  
R. Paus ◽  
...  
Keyword(s):  
Mouse Model ◽  
Platelet Rich Plasma ◽  
Hair Shaft ◽  
Androgenetic Alopecia ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Terminal Hair ◽  
Hair Regrowth ◽  
Shaft Diameter

scholarly journals P06.07 In vivo studies of immunomodulatory a-CTLA-4 antibody in a humanized mouse model

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A22.1-A22
Author(s):  
C Reitinger ◽  
F Nimmerjahn
Keyword(s):  
Immune System ◽  
Mouse Model ◽  
Cancer Immunotherapy ◽  
Model Systems ◽  
Checkpoint Control ◽  
Human Immune System ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Human Immune

BackgroundRecent findings in cancer immunotherapy have reinforced the hypothesis that the immune system is able to control most cancers. Immunomodulatory antibodies can enhance immune responses, having the potential to generate anti-cancer immunity.1–4Materials and MethodsMost current studies addressing this question are performed in murine mouse model systems or use in vitro culture systems, which do not reflect the human in vivo situation, potentially leading to results that cannot be fully translated into human cancer therapy. Therefore, it is necessary to establish a new mouse model, which allows the study of cancer immunotherapy in the context of a human immune system. We focused on the establishment of a humanized mouse model, in which different immunomodulatory antibodies can be tested in the presence of a human immune system.ResultsFirst experiments concerning the suitability to test immunomodulatory antibodies in the humanized mouse model, revealed that effects of checkpoint-control antibody a-CTLA-4 were similar to the effects seen in patients of clinical studies. To analyse the anti-tumor activities of immunomodulatory antibodies in vivo we are establishing a human melanoma-like tumor model in humanized mice.ConclusionsThis enables us to test the efficacy of immunomodulatory agonistic antibodies (such as CP-870,893) and checkpoint control antibodies (such as anti-CTLA-4) in eliminating a melanoma-like tumor. Furthermore, parameters like tumor infiltrating human cells und cytokine/chemokine production can be analysed.ReferencesSchuster M, Nechansky A, Loibner H. Cancer immunotherapy. Biotechnol J 2006;1:138–147.Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature rev 2011;480:480–489.Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Annals of Oncology 2012;23:vii6–vii9.Langer LF, Clay TM, Morse MA. Update on anti-CTLA-4 in clinical trials. Expert Opin Biol Ther 2007;8:1245–1256.Disclosure InformationC. Reitinger: None. F. Nimmerjahn: None.

scholarly journals A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Maria M. Klicznik ◽  
Ariane Benedetti ◽  
Laura M. Gail ◽  
Suraj R. Varkhande ◽  
Raimund Holly ◽  
...  
Keyword(s):  
T Cells ◽  
Mouse Model ◽  
Human Skin ◽  
Memory T Cells ◽  
Humanized Mouse ◽  
Humanized Mouse Model

In Vivo Anti-MicroRNA Treatment in a Humanized Mouse Model for Allograft Vasculopathy

2017 ◽  
Vol 36 (4) ◽  
pp. S446
Author(s):  
M. Huibers ◽  
L. Qin ◽  
G. Li ◽  
J. Renes ◽  
C. Venema ◽  
...  
Keyword(s):  
Mouse Model ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Allograft Vasculopathy

scholarly journals Human anti-CAIX antibodies mediate immune cell inhibition of renal cell carcinoma in vitro and in a humanized mouse model in vivo

2015 ◽  
Vol 14 (1) ◽  
Author(s):  
De-Kuan Chang ◽  
Raymond J. Moniz ◽  
Zhongyao Xu ◽  
Jiusong Sun ◽  
Sabina Signoretti ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Mouse Model ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Immune Cell ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Cell Inhibition

scholarly journals Evaluation of 4-Amino 2-Anilinoquinazolines against Plasmodium and Other Apicomplexan Parasites In Vitro and in a P. falciparum Humanized NOD-scid IL2Rγnull Mouse Model of Malaria

2018 ◽  
Vol 63 (3) ◽  
Author(s):  
Paul R. Gilson ◽  
William Nguyen ◽  
William A. Poole ◽  
Jose E. Teixeira ◽  
Jennifer K. Thompson ◽  
...  
Keyword(s):  
Mouse Model ◽  
Babesia Bovis ◽  
Parasite Line ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Content Type ◽  
Apicomplexan Parasites ◽  
Micromolar Range

ABSTRACT A series of 4-amino 2-anilinoquinazolines optimized for activity against the most lethal malaria parasite of humans, Plasmodium falciparum, was evaluated for activity against other human Plasmodium parasites and related apicomplexans that infect humans and animals. Four of the most promising compounds from the 4-amino 2-anilinoquinazoline series were equally as effective against the asexual blood stages of the zoonotic P. knowlesi, suggesting that they could also be effective against the closely related P. vivax, another important human pathogen. The 2-anilinoquinazoline compounds were also potent against an array of P. falciparum parasites resistant to clinically available antimalarial compounds, although slightly less so than against the drug-sensitive 3D7 parasite line. The apicomplexan parasites Toxoplasma gondii, Babesia bovis, and Cryptosporidium parvum were less sensitive to the 2-anilinoquinazoline series with a 50% effective concentration generally in the low micromolar range, suggesting that the yet to be discovered target of these compounds is absent or highly divergent in non-Plasmodium parasites. The 2-anilinoquinazoline compounds act as rapidly as chloroquine in vitro and when tested in rodents displayed a half-life that contributed to the compound’s capacity to clear P. falciparum blood stages in a humanized mouse model. At a dose of 50 mg/kg of body weight, adverse effects to the humanized mice were noted, and evaluation against a panel of experimental high-risk off targets indicated some potential off-target activity. Further optimization of the 2-anilinoquinazoline antimalarial class will concentrate on improving in vivo efficacy and addressing adverse risk.

scholarly journals RARE-01. IN VIVO IMMUNOMODULATING EFFECT OF LXR-623 AND ITS SYNERGISM WITH CHECKPOINT BLOCKADE AGAINST CHORDOMAS IN A HUMANIZED MOUSE MODEL

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi236-vi236
Author(s):  
Wataru Ishida ◽  
Riccardo Serra ◽  
Noah Gorelick ◽  
Yuanxuan Xia ◽  
Joshua Casaos ◽  
...  
Keyword(s):  
Mouse Model ◽  
Checkpoint Blockade ◽  
Immunomodulating Effect ◽  
Humanized Mouse ◽  
Humanized Mouse Model

scholarly journals Blocking HIV-1 Infection by Chromosomal Integrative Expression of Human CD4 on the Surface of Lactobacillus acidophilus ATCC 4356

2019 ◽  
Vol 93 (8) ◽  
Author(s):  
Wenzhong Wei ◽  
Joshua Wiggins ◽  
Duoyi Hu ◽  
Vladimir Vrbanac ◽  
Dane Bowder ◽  
...  
Keyword(s):  
Mouse Model ◽  
Lactobacillus Acidophilus ◽  
Sexual Transmission ◽  
Effective Vaccine ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Antiviral Proteins ◽  
Hiv 1

ABSTRACT Lactobacillus bacteria are potential delivery vehicles for biopharmaceutical molecules because they are well-recognized as safe microorganisms that naturally inhabit the human body. The goal of this study was to employ these lactobacilli to combat human immunodeficiency virus type 1 (HIV-1) infection and transmission. By using a chromosomal integration method, we engineered Lactobacillus acidophilus ATCC 4356 to display human CD4, the HIV-1 receptor, on the cell surface. Since human CD4 can bind to any infectious HIV-1 particles, the engineered lactobacilli can potentially capture HIV-1 of different subtypes and prevent infection. Our data demonstrate that the CD4-carrying bacteria are able to adsorb HIV-1 particles and reduce infection significantly in vitro and also block intrarectal HIV-1 infection in a humanized mouse model in preliminary tests in vivo. Our results support the potential of this approach to decrease the efficiency of HIV-1 sexual transmission. IMPORTANCE In the absence of an effective vaccine, alternative approaches to block HIV-1 infection and transmission with commensal bacteria expressing antiviral proteins are being considered. This report provides a proof-of-concept by using Lactobacillus bacteria stably expressing the HIV-1 receptor CD4 to capture and neutralize HIV-1 in vitro and in a humanized mouse model. The stable expression of antiviral proteins, such as CD4, following genomic integration of the corresponding genes into this Lactobacillus strain may contribute to the prevention of HIV-1 sexual transmission.

Disregulated Osteogenesis By Mesenchymal Stromal Cells (MSC) After In Vivo Exposure To Multiple Myeloma: Studies In a Novel Humanized Mouse Model For Bone Remodelling In Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1906-1906
Author(s):  
Richard W.J. Groen ◽  
Willy A. Noort ◽  
Jessica Sigmans ◽  
Aniek van Stralen ◽  
Linda Aalders ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Mouse Model ◽  
Bone Formation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Hybrid Scaffolds

Abstract Multiple myeloma (MM), a B-cell neoplasm characterized by a clonal expansion of malignant plasma cells in the bone marrow (BM), is accompanied by osteolytic lesions and/or diffuse osteopenia in up to 90% of the patients. Even after successful treatment, these MM-induced bone lesions do not normalize. We hypothesized that this might be caused by MM-induced irreversible impairment of the osteoblast function in the BM microenvironment. To study this bone remodeling processes in MM we used a recently developed, humanized mouse model of MM that allows engraftment and outgrowth of patient MM (pMM) cells in a humanized BM niche. To this end, ceramic scaffolds are seeded with culture-expanded human mesenchymal stromal cells (MSCs) from human BM, differentiated in vitro to osteoblasts for 1 week, then implanted subcutaneously in immune-deficient RAG2-/-gc-/--mice and after 6-8 weeks a layer of human bone is deposited on the surface of the scaffolds. Following the injection of luciferase-GFP gene marked primary MM cells (pMM), this results in homing and outgrowth of pMM in the scaffolds (Groen et al., Blood 2012). Here we describe a modification of this in vivo model, by co-implanting MSC loaded scaffolds, with pMM cells adhered to the hybrid scaffolds, at one side of the mouse, and with hybrid scaffolds only (without pMM) at the other side of the mouse. At this contra-lateral location bone formation can take place undisturbed (i.e., not affected by the presence of MM) and serves as an internal control for the osteogenic potential of the osteoblasts. Thus this model allows us to study bidirectional interactions between pMM cells and the osteoblast and the resulting inhibition of osteogenesis. Here we report that outgrowth pMM cells indeed resulted in on average 50-75% decrease in bone formation, and, using bioluminescence imaging, we found an inverse correlation between the size of the tumor and the amount of bone formation: with increasing tumor size, the amount of bone formed was less. Human AML growing in the scaffolds (serving as control) does not influence the bone forming process. At the end of the experiment when we analyzed gene expression in the human stromal cells (CD73+ CD90+ CD105+) that we cultured from scaffolds containing pMM tumors, we found a significant reduction in expression of transcripts for alkaline phosphatase (ALP), collagen1A1 (colA1), osteoglycin (OGN), osteomodulin (OMD), and abnormal spindle-like microcephaly associated (ASPM), genes that have been implicated in osteogenesis. These data suggest that pMM cells interfere with the osteogenic differentiation of MSCs in the context of an in vivo biocompatible scaffold engineered to simulate the human BM microenvironment. Taken together, our data show that co-implanting MSCs together with the pMM cells can serve as a model to study the effect of pMM cells on osteogenesis, which provides a tool to unravel the mutual interaction between MM cells and the bone marrow microenvironment. Disclosures: No relevant conflicts of interest to declare.

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