Generation and Homing of iPSC-Derived Hematopoietic Cells In Vivo

Chou, Bin Kuan; Ye, Zhaohui; Cheng, Linzhao

doi:10.1038/mt.2013.129

Cited by 7 publications

(7 citation statements)

References 9 publications

(13 reference statements)

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“…Here, progress in the generation of engraftable iHSCs from iPSCs (reviewed in Chou et al, 2013) in combination with iHeps derived from the same iPSC donor may solve this issue. Additionally, since human immune responses are generally weak in HSC-transplanted mice, further modifications will be needed to improve both the cellular complexity and functionality of the engrafted human immune system.…”

Section: Humanized Mouse Avatars To Dissect Patient-specific (Immumentioning

confidence: 99%

Murine models of hepatitis C: What can we look forward to?

Schaewen

Ploß

2014

Antiviral Research

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The study of interactions between hepatitis C virus (HCV) with its mammalian host, along with the development of more effective therapeutics and vaccines has been delayed by the lack of a suitable small animal model. HCV readily infects only humans and chimpanzees, which poses logistic, economic and ethical challenges with analyzing HCV infection in vivo. Progress has been made in understanding the determinants that dictate HCV’s narrow host range providing a blueprint for constructing a mouse model with inheritable susceptibility to HCV infection. Indeed, genetically humanized mice were generated that support viral uptake, replication and production of infectious virions – albeit at low levels. These efforts are complemented with attempts to select for viral variants that are inherently more capable of replicating in non-human species. In parallel, engraftment of relevant human tissues into improved xenorecipients is being continuously refined. Incorporating advances in stem-cell-biology and tissue engineering may allow the generation of patient-specific humanized mice. Construction of such mouse “avatars” may allow analyzing functionally patient-specific differences with respect to susceptibility to infection, disease progression and responses to treatment. In this review, we discuss the three, before mentioned approaches to overcome current species barriers and generate a small animal model for HCV infection, i.e. genetic modification of mice to increase their susceptibility to the virus; genetic modification of HCV, to increase its pathogenicity for mice; and the introduction of human liver and immune cells into immunodeficient mice, to create “humanized” mice. Although in the foreseeable future there will not be a single model that perfectly mimics the natural course of HCV in humans there is reason for optimism. The spectrum of murine animal models for hepatitis C provides a broad arsenal for analyzing the disease. These models may play an important role by prioritizing vaccine candidates and possibly refining combination anti-viral drug therapies. This article forms part of a symposium in Anti-viral Research on “Hepatitis C: next steps toward global eradication.”

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Section: Humanized Mouse Avatars To Dissect Patient-specific (Immumentioning

confidence: 99%

Murine models of hepatitis C: What can we look forward to?

Schaewen

Ploß

2014

Antiviral Research

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“…Recent advances in induced pluripotent stem cell (iPSC)-derived hepatocyte engraftment of human liver-chimeric mice and their subsequent HBV infection are very promising . However, reports on iPSC-derived HSC and their engraftment are, to date, very limited . If this were overcome, the resulting model would allow for an indefinite cell source for xenotransplantation.…”

Section: Discussionmentioning

confidence: 99%

“…175 However, reports on iPSC-derived HSC and their engraftment are, to date, very limited. 176 If this were overcome, the resulting model would allow for an indefinite cell source for xenotransplantation.…”

Section: ■ Xenotranplantation Models For Hbvmentioning

confidence: 99%

In Vivo Model Systems for Hepatitis B Virus Research

et al. 2018

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Hepatitis B virus (HBV) affects more than 257 million people globally, resulting in progressively worsening liver disease, manifesting as fibrosis, cirrhosis, and hepatocellular carcinoma. The exceptionally narrow species tropism of HBV restricts its natural hosts to humans and non-human primates, including chimpanzees, gorillas, gibbons, and orangutans. The unavailability of completely immunocompetent small-animal models has contributed to the lack of curative therapeutic interventions. Even though surrogates allow the study of closely related viruses, their host genetic backgrounds, immune responses, and molecular virology differ from those of HBV. Various different models, based on either pure murine or xenotransplantation systems, have been introduced over the past years, often making the choice of the optimal model for any given question challenging. Here, we offer a concise review of in vivo model systems employed to study HBV infection and steps in the HBV life cycle or pathogenesis.

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“…Although not fully understood, the presumption is that signals emanating from the in vivo microenvironment of the developing teratoma facilitated HSC development in this setting. Nonetheless, the use of teratoma-based methodologies to derive HSCs for the clinic are, at present, not feasible owing to the very low efficiency of HSC generation, and safety issues related to zoonosis and the residual undifferentiated iPS cells [7]. Recent efforts to define cell types capable of establishing niche-like environments able to support productive and ongoing hematopoiesis may offer an alternative to using teratomas in deriving HSC from PSCs [8, 9].…”

Section: Recapitulating Hematopoietic Ontogeny To Generate Hscs From mentioning

confidence: 99%

Progress and obstacles towards generating hematopoietic stem cells from pluripotent stem cells

Lee

Dykstra

Sackstein

et al. 2015

Current Opinion in Hematology

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Purpose of review Human pluripotent stem cells (PSCs) have the potential to provide an inexhaustible source of hematopoietic stem cells (HSCs) that could be used in disease modeling and in clinical applications such as transplantation. Although the goal of deriving definitive HSCs from PSCs has not been achieved, recent studies indicate that progress is being made. This review will provide information on the current status of deriving HSCs from PSCs, and will highlight existing challenges and obstacles. Recent findings Recent strides in HSC generation from PSCs has included derivation of developmental intermediates, identification of transcription factors and small molecules that support hematopoietic derivation, and the development of strategies to recapitulate niche-like conditions. Summary Despite considerable progress in defining the molecular events driving derivation of hematopoietic progenitor cells (HPCs) from PSCs, the generation of robust transplantable HSCs from PSCs remains elusive. We propose that this goal can be facilitated by better understanding of the regulatory pathways governing HSC identity, development of HSC supportive conditions, and examining the marrow homing properties of PSC-derived HSCs.

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Generation and Homing of iPSC-Derived Hematopoietic Cells In Vivo

Cited by 7 publications

References 9 publications

Murine models of hepatitis C: What can we look forward to?

Murine models of hepatitis C: What can we look forward to?

In Vivo Model Systems for Hepatitis B Virus Research

Progress and obstacles towards generating hematopoietic stem cells from pluripotent stem cells

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