Risks and Mechanisms of Oncological Disease Following Stem Cell Transplantation

Anisimov, S. V.; Morizane, Asuka; Correia, Ana Sofia

doi:10.1007/s12015-010-9134-5

Cited by 18 publications

(13 citation statements)

References 149 publications

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“…Other strategies to prevent overgrowth of grafted stem cells include prolonged differentiation, selection of more mature cells using fluorescence-activated or magnetic-activated cell sorting, introduction of suicide genes, and irradiation [36]; these approaches, however, require complicated procedures or long periods to prepare donor cells. Compared with these techniques, GSI treatment is a simple and inexpensive procedure that can be used in combination with other promising options, such as cell sorting, to optimize the safety of cell replacement therapies using iPSCs.…”

Section: C-secretase Inhibitors Prevent Neural Overgrowthmentioning

confidence: 99%

γ-Secretase Inhibitors Prevent Overgrowth of Transplanted Neural Progenitors Derived from Human-Induced Pluripotent Stem Cells

Ogura

Morizane

Nakajima

et al. 2013

Stem Cells and Development

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Although transplanted pluripotent stem cell-derived neurons can contribute to functional recovery in animal models of Parkinson's disease, the risk of tumor formation hinders clinical applications of this approach. Removing undifferentiated cells from the donor population is critical to reduce tumorigenesis. Moreover, immature neural progenitors in transplants can proliferate unpredictably, resulting in neural overgrowth and long-term risks of compressing the surrounding host tissue. Because Notch signaling plays a role in maintaining the multipotency and proliferative capacity of neural progenitors, we used γ-secretase inhibitors (GSIs) to dampen Notch signaling in human-induced pluripotent stem cell-derived neural progenitors before transplantation and examined the effects on the growth of proliferative grafts. We observed a marked reduction in the percentage of dividing cells and increased neuronal maturation in GSI-treated samples in vitro. Next, grafts were transplanted into the striata of nonobese diabetic/severe combined immune deficiency mice. Histological analyses performed 8 weeks after the operation showed that grafts pretreated with GSIs--N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester or compound E--were significantly smaller than control samples. Immunohistologic analyses revealed that briefly treating the donor population with GSIs not only reduced the graft volume, but also altered the composition of the graft; control grafts showed neural overgrowth with numerous PAX6+ and Ki67+ neural rosettes, whereas GSI-treated samples developed into mature neuronal grafts containing primarily Tubβ3+ cells. These results suggest that pretreating potentially proliferative progenitors with GSIs may improve the safety of cell replacement therapies using pluripotent stem cells.

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Section: C-secretase Inhibitors Prevent Neural Overgrowthmentioning

confidence: 99%

γ-Secretase Inhibitors Prevent Overgrowth of Transplanted Neural Progenitors Derived from Human-Induced Pluripotent Stem Cells

Ogura

Morizane

Nakajima

et al. 2013

Stem Cells and Development

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“…Notably, as few as two mouse ESCs [43] or 245 human ESCs [44] were reported to be able to form teratomas in immunodeficient mice. Importantly, teratomas and teratocarcinomas are not the only tumors that can form out of stem cell-derived grafts [19]. Transplantation of grafts containing non-pluripotent lineage committed stem cells might lead to growth of tumors that are more restricted in their tissue composition [36, 45, 46].…”

Section: The Relation Of Pluripotency and Tumorigenicity In Stem Cellmentioning

confidence: 99%

Effects of histocompatibility and host immune responses on the tumorigenicity of pluripotent stem cells

Dressel

2011

Semin Immunopathol

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Pluripotent stem cells hold great promises for regenerative medicine. They might become useful as a universal source for a battery of new cell replacement therapies. Among the major concerns for the clinical application of stem cell-derived grafts are the risks of immune rejection and tumor formation. Pluripotency and tumorigenicity are closely linked features of pluripotent stem cells. However, the capacity to form teratomas or other tumors is not sufficiently described by inherited features of a stem cell line or a stem cell-derived graft. The tumorigenicity always depends on the inability of the recipient to reject the tumorigenic cells. This review summarizes recent data on the tumorigenicity of pluripotent stem cells in immunodeficient, syngeneic, allogeneic, and xenogeneic hosts. The effects of immunosuppressive treatment and cell differentiation are discussed. Different immune effector mechanisms appear to be involved in the rejection of undifferentiated and differentiated cell populations. Elements of the innate immune system, such as natural killer cells and the complement system, which are active also in syngeneic recipients, appear to preferentially reject undifferentiated cells. This effect could reduce the risk of tumor formation in immunocompetent recipients. Cell differentiation apparently increases susceptibility to rejection by the adaptive immune system in allogeneic hosts. The current data suggest that the immune system of the recipient has a major impact on the outcome of pluripotent stem cell transplantation, whether it is rejection, engraftment, or tumor development. This has to be considered when the results of experimental transplantation models are interpreted and even more when translation into clinics is planned.

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“…In addition, clinical evidences supporting a potential efficacy and safety of utilizing autologous PDL cells in treating human periodontitis . However, all the aforementioned PDLSCs‐based therapies have several drawbacks, such as causing trauma, increasing donor site morbidity, time and cost‐consuming, and having the risk of contamination . The up‐to‐date strategy of in situ tissue engineering can overcome the above shortcomings, which harnesses the innate regenerative potential of the body and focuses on the recruitment of endogenous stem cells to the site of injury to enhance healing .…”

Section: Introductionmentioning

confidence: 99%

Sequential application of bFGF and BMP‐2 facilitates osteogenic differentiation of human periodontal ligament stem cells

Kang

Liang

et al. 2019

J of Periodontal Research

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Background and Objectives Basic fibroblast growth factor (bFGF) promotes cells proliferation and chemotaxis and maintains stemness while inhibits mineralized nodule formation. Bone morphogenetic protein 2 (BMP‐2) shows great potential in promoting bone formation. However, sequential application of these two growth factors on periodontal ligament stem cells (PDLSCs) has not been explored. In this study, we aimed to identify the optimal concentration and time of bFGF on PDLSCs proliferation, migration and then investigate the sequential delivery of bFGF and BMP‐2 on osteogenic differentiation of PDLSCs in vitro. Materials and Methods Periodontal ligament stem cells were isolated by limiting dilution method. Dose‐dependent additive effects of bFGF and BMP‐2 on PDLSCs were detected. Cell counting assay, cell migration assay, alkaline phosphatase (ALP) activity assay, Alizarin red staining, quantitative real‐time polymerase chain reaction (qRT‐PCR), and western blot analysis were used to determine different application modalities of bFGF and BMP‐2 on proliferation, migration, and osteogenic differentiation of PDLSCs. Results 50 ng/mL bFGF significantly promoted PDLSCs proliferation and chemotaxis while time‐dependently inhibited BMP‐2 induced ALP activity. Sequential application of 25 ng/mL bFGF for first 3 days and followed with 50 ng/mL BMP‐2 for another 9, 18, and 25 days significantly promoted PDLSCs osteogenic differentiation. Compared with bFGF and BMP‐2 simultaneous group, sequential application of bFGF and BMP‐2 group significantly enhanced ALP activity, osteogenesis‐related genes and proteins expression and mineral deposition. Conclusion Sequential application of bFGF and BMP‐2 synergistically promoted osteogenic differentiation of PDLSCs, and this sequential application modality of growth factors would provide a new strategy for periodontal regeneration.

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Risks and Mechanisms of Oncological Disease Following Stem Cell Transplantation

Cited by 18 publications

References 149 publications

γ-Secretase Inhibitors Prevent Overgrowth of Transplanted Neural Progenitors Derived from Human-Induced Pluripotent Stem Cells

γ-Secretase Inhibitors Prevent Overgrowth of Transplanted Neural Progenitors Derived from Human-Induced Pluripotent Stem Cells

Effects of histocompatibility and host immune responses on the tumorigenicity of pluripotent stem cells

Sequential application of bFGF and BMP‐2 facilitates osteogenic differentiation of human periodontal ligament stem cells

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