PDGFB-expressing mesenchymal stem cells improve human hematopoietic stem cell engraftment in immunodeficient mice

Yin, Xiuxiu; Hu, Linping; Zhang, Yawen; Zhu, Caiying; Cheng, Hui; Xie, Xiaowei; Shi, Ming; Zhu, Ping; Zhao, Xueying; Chen, Wanqiu; Zhang, Lu; Arakaki, Cameron; Hao, Sha; Wang, Mei; Cao, Wenbin; Ma, Shihui; Zhang, Xiaobing; Cheng, Tao

doi:10.1038/s41409-019-0766-z

Cited by 31 publications

(48 citation statements)

References 44 publications

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“…Overall, co-transplantation of the BM-derived MSCs into humanized mice can improve human HSPC maintenance and expansion, and improve reconstitution of the human hemato-lymphoid system in humanized mice. Furthermore, recent studies have used genetically engineered MSCs to deliver additional human factors to support human hematopoiesis, or to facilitate the expansion and maintenance of HSPCs to allow serial transplantation and generation of larger quantities of humanized mice ( 118 , 119 ).…”

Section: Principle #3: Supporting the Development Of Engrafted Human mentioning

confidence: 99%

Building the Next Generation of Humanized Hemato-Lymphoid System Mice

et al. 2021

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Since the late 1980s, mice have been repopulated with human hematopoietic cells to study the fundamental biology of human hematopoiesis and immunity, as well as a broad range of human diseases in vivo. Multiple mouse recipient strains have been developed and protocols optimized to efficiently generate these “humanized” mice. Here, we review three guiding principles that have been applied to the development of the currently available models: (1) establishing tolerance of the mouse host for the human graft; (2) opening hematopoietic niches so that they can be occupied by human cells; and (3) providing necessary support for human hematopoiesis. We then discuss four remaining challenges: (1) human hematopoietic lineages that poorly develop in mice; (2) limited antigen-specific adaptive immunity; (3) absent tolerance of the human immune system for its mouse host; and (4) sub-functional interactions between human immune effectors and target mouse tissues. While major advances are still needed, the current models can already be used to answer specific, clinically-relevant questions and hopefully inform the development of new, life-saving therapies.

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Section: Principle #3: Supporting the Development Of Engrafted Human mentioning

confidence: 99%

Building the Next Generation of Humanized Hemato-Lymphoid System Mice

et al. 2021

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“…Secreted PDGF-BB is involved in cancer progression via multiple mechanisms. PDGF-BB induces the stem cell phenotype either by accelerating the maturation of collagen chains through increased LOX activity 35 or by inducing both perivascular and satellite cell gene expression to acquire improved migration of human hematopoietic cells 36,37 . Our data showed that PDGFB silencing abrogated the RASSF1A depletion-induced malignant phenotypes of NPC cells.…”

Section: Discussionmentioning

confidence: 99%

RASSF1A inhibits PDGFB-driven malignant phenotypes of nasopharyngeal carcinoma cells in a YAP1-dependent manner

et al. 2020

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Nasopharyngeal carcinoma (NPC) is a highly aggressive tumor characterized by distant metastasis. Deletion or down-regulation of the tumor suppressor protein ras-association domain family protein1 isoform A (RASSF1A) has been confirmed to be a key event in NPC progression; however, little is known about the effects or underlying mechanism of RASSF1A on the malignant phenotype. In the present study, we observed that RASSF1A expression inhibited the malignant phenotypes of NPC cells. Stable silencing of RASSF1A in NPC cell lines induced self-renewal properties and tumorigenicity in vivo/in vitro and the acquisition of an invasive phenotype in vitro. Mechanistically, RASSF1A inactivated Yes-associated Protein 1 (YAP1), a transcriptional coactivator, through actin remodeling, which further contributed to Platelet Derived Growth Factor Subunit B (PDGFB) transcription inhibition. Treatment with ectopic PDGFB partially increased the malignancy of NPC cells with transient knockdown of YAP1. Collectively, these findings suggest that RASSF1A inhibits malignant phenotypes by repressing PDGFB expression in a YAP1-dependent manner. PDGFB may serve as a potential interest of therapeutic regulators in patients with metastatic NPC.

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“…Various modi cations of MSCs have been attempted to improve their survival rates and therapeutic e cacy [31,32,34,35]. Attempts to improve stem cell survival, metabolism, or migration ability have focused on genetic modi cations to knock-out or knock-in speci c genes [36][37][38]. However, the clinical application of genetically-modi ed MSCs is associated with the risk of unexpected genetic mutations resulting in tumor formation [39].…”

Section: Discussionmentioning

confidence: 99%

Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects

Park

Kim²,

Kwon³

et al. 2020

Preprint

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BackgroundMesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of Alzheimer’s disease (AD). Previous studies suggested that the co-culture of human MSCs with AD in an in vitro model reduced the expression of amyloid-beta 42 (Aβ42) in the medium as well as the overexpression of amyloid-beta (Aβ )-degrading enzymes such as neprilysin (NEP).MethodsIn this study, we focused on the role of primed MSCs (human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) exposed to an AD cell line via a co-culture system) in reducing the levels of Aβ and inhibiting cell death. ResultsWe demonstrated that mouse groups treated with naïve MSCs and primed MSCs showed significant reductions in cell death, ubiquitin conjugate levels, and Aβ levels, but the effects were greater in primed MSCs. Also, mRNA sequencing data analysis indicated that high levels of TGF-β induced primed-MSCs. Furthermore, treatment with TGF-β reduced Aβ expression in an AD transgenic mouse model. ConclusionAD environmental preconditioning is a promising strategy to reduce cell death and ubiquitin conjugate levels and maintain the stemness of MSCs. Further, these data suggest that human WJ-MSCs exposed to an AD environment may represent a promising and novel therapy for AD.

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PDGFB-expressing mesenchymal stem cells improve human hematopoietic stem cell engraftment in immunodeficient mice

Cited by 31 publications

References 44 publications

Building the Next Generation of Humanized Hemato-Lymphoid System Mice

Building the Next Generation of Humanized Hemato-Lymphoid System Mice

RASSF1A inhibits PDGFB-driven malignant phenotypes of nasopharyngeal carcinoma cells in a YAP1-dependent manner

Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects

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