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human umbilical cord-derived mesenchymal stem cells to differentiate into sweat gland-like cells: a preclinical

Siming Yang, Kui Ma, Changjiang Feng, Yan Wu, Yao Wang, Sha Huang, Xiaobing Fu

Frontiers of Medicine 2013, Volume 7, Issue 3,   Pages 345-353 doi: 10.1007/s11684-013-0282-2

Abstract:

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) possess various advantageous properties, including self-renewal, extended proliferation potential, multi-lineage differentiation potential and capacity for differentiating into sweat gland-like cells in certain conditions. However, little is known about the effect of clinical-grade culture conditions on these properties and on the differentiative potential of hUC-MSCs. In this study, we sought to investigate the properties of hUC-MSCs expanded with animal serum free culture media (ASFCM) in order to determine their potential for differentiation into sweat gland-like cells. We found that primary cultures of hUC-MSCs could be established with ASFCM. Moreover, cells cultured in ASFCM showed vigorous proliferation comparable to those of cells grown in classical culture conditions containing fetal bovine serum (FBS). Morphology of hUC-MSCs cultured in ASFCM was comparable to those of cells grown under classical culture conditions, and hUC-MSCs grown in both of the two culture conditions tested showed the typical antigen profile of MSCs—positive for CD29, CD44, CD90, and CD105, and negative for CD34 and CD45, as expected. Chromosomal aberration assay revealed that the cells were stable after long-term culture under both culture conditions. Like normal cultured MSCs, hUC-MSCs induced under ASFCM conditions exhibited expression of the same markers (CEA, CK14 and CK19) and developmental genes (EDA and EDAR) that are characteristic of normal sweat gland cells. Taken together, our findings indicate that the classical culture medium used to differentiate hUC-MSCs into sweat gland-like cells can be replaced safely by ASFCM for clinical purposes.

Keywords： umbilical cord     mesenchymal stem cells     sweat gland     preclinical    

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non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical

Frontiers of Medicine doi: 10.1007/s11684-023-0996-8

Abstract: OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40–OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.

Keywords： BGB-A445     OX40     agonistic antibody     OX40L noncompetitive    

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Patient-derived xenograft platform of OSCC: a renewable human bio-bank for preclinical cancer research

Shuyang Sun,Zhiyuan Zhang

Frontiers of Medicine 2016, Volume 10, Issue 1,   Pages 104-110 doi: 10.1007/s11684-016-0432-4

Abstract: Sophisticated preclinical models that fully represent intra- and inter-tumoral heterogeneity are requiredretain the histological and genetic features of their donor tumors have been shown to be the preferred preclinicaltool in translational cancer research compared with other conventional preclinical models.In this paper, we discuss the establishment, characterization, and preclinical applications of the PDXAlthough various limitations still exist, this preclinical approach should be further tested and improved

Keywords： patient-derived xenograft models     personalized medicine     co-clinical trial     patient stratification     oral squamous cell carcinoma    

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Recent Progress in Cartilage Tissue Engineering—Our Experience and Future Directions

Yu Liu, Guangdong Zhou, Yilin Cao

Engineering 2017, Volume 3, Issue 1,   Pages 28-35 doi: 10.1016/J.ENG.2017.01.010

Abstract: The statuses of preclinical animal investigations and of the clinical translation of engineered cartilage

Keywords： Cartilage tissue engineering     Preclinical immunocompetent animal     investigation     Clinical translation     Orthopedic    

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Preclinical characterization and comparison between CD3/CD19 bispecific and novel CD3/CD19/CD20 trispecific

Frontiers of Medicine 2022, Volume 16, Issue 1,   Pages 139-149 doi: 10.1007/s11684-021-0835-8

Abstract: The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.

Keywords： B-cell acute lymphoblastic leukemia     bispecific antibody     trispecific antibody     CD19     CD20    

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Artificial Bear Bile: A Novel Approach to Balancing Medical Requirements and Animal Welfare

Yong Li,Yuhong Huang,Nan Feng,Heping Zhang,Jing Qu,Shuanggang Ma,Yunbao Liu,Jiang Li,Shaofeng Xu,Ling Wang,Mi Zhang,Jie Cai,Weiping Wang,Ru Feng,Hang Yu,Bo Yu,Dailiang Liang,Heping Qin,Suxiang Luo,Yanfen Li,

Engineering doi: 10.1016/j.eng.2023.09.017

Abstract: Comprehensive preclinical efficacy evaluations have demonstrated the equivalence of the therapeutic effectsFurthermore, preclinical toxicological assessment and phase Ⅰ clinical trials show that the safety of

Keywords： Artificial bear bile     Chemical profile     Formula optimization     Pharmacodynamic consistency     Preclinical toxicological    

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Title Author Date Type Operation

human umbilical cord-derived mesenchymal stem cells to differentiate into sweat gland-like cells: a preclinical

Siming Yang, Kui Ma, Changjiang Feng, Yan Wu, Yao Wang, Sha Huang, Xiaobing Fu

Journal Article

non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical

Journal Article

Patient-derived xenograft platform of OSCC: a renewable human bio-bank for preclinical cancer research

Shuyang Sun,Zhiyuan Zhang

Journal Article

Recent Progress in Cartilage Tissue Engineering—Our Experience and Future Directions

Yu Liu, Guangdong Zhou, Yilin Cao

Journal Article

Preclinical characterization and comparison between CD3/CD19 bispecific and novel CD3/CD19/CD20 trispecific

Journal Article

Artificial Bear Bile: A Novel Approach to Balancing Medical Requirements and Animal Welfare

Yong Li,Yuhong Huang,Nan Feng,Heping Zhang,Jing Qu,Shuanggang Ma,Yunbao Liu,Jiang Li,Shaofeng Xu,Ling Wang,Mi Zhang,Jie Cai,Weiping Wang,Ru Feng,Hang Yu,Bo Yu,Dailiang Liang,Heping Qin,Suxiang Luo,Yanfen Li,

Journal Article