Concise Review: Induced Pluripotent Stem Cells and Lineage Reprogramming: Prospects for Bone Regeneration

Illich, Damir J.; Demir, Necati; Stojković, Miodrag; Scheer, Martin; Rothamel, Daniel; Neugebauer, Jörg; Hescheler, Jürgen; Zöller, Joachim E.

doi:10.1002/stem.611

Cited by 55 publications

(40 citation statements)

References 127 publications

(165 reference statements)

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“…The relationship between DPPSCs and iPS cells should also be investigated. The induction of iPS cells seems to be easier from stem cells than from differentiated cells (Illich et al, 2011). It could be that a reprogramming process occurs in DPPSCs, but not in differentiated dermal fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Dental Pulp of the Third Molar: A New Source of Pluripotent-like Stem Cells

Atari

Gil-Recio

Fabregat

et al. 2012

Journal of Cell Science

109

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SummaryDental pulp is particularly interesting in regenerative medicine because of the accessibility and differentiation potential of the tissue. Dental pulp has an early developmental origin with multi-lineage differentiation potential as a result of its development during childhood and adolescence. However, no study has previously identified the presence of stem cell populations with embryonic-like phenotypes in human dental pulp from the third molar. In the present work, we describe a new population of dental pulp pluripotent-like stem cells (DPPSCs) that were isolated by culture in medium containing LIF, EGF and PDGF. , and they show genetic stability in vitro based on genomic analysis with a newly described CGH technique. Interestingly, DPPSCs were able to form both embryoid-body-like structures (EBs) in vitro and teratoma-like structures that contained tissues derived from all three embryonic germ layers when injected in nude mice. We examined the capacity of DPPSCs to differentiate in vitro into tissues that have similar characteristics to mesoderm, endoderm and ectoderm layers in both 2D and 3D cultures. We performed a comparative RT-PCR analysis of GATA4, GATA6, MIXL1, NANOG, OCT3/4, SOX1 and SOX2 to determine the degree of similarity between DPPSCs, EBs and human induced pluripotent stem cells (hIPSCs). Our analysis revealed that DPPSCs, hIPSC and EBs have the same gene expression profile. Because DPPSCs can be derived from healthy human molars from patients of different sexes and ages, they represent an easily accessible source of stem cells, which opens a range of new possibilities for regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Dental Pulp of the Third Molar: A New Source of Pluripotent-like Stem Cells

Atari

Gil-Recio

Fabregat

et al. 2012

Journal of Cell Science

109

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“…These approaches are still in their infancy as new vectors are required to prevent tumorigenesis that may be due to insertional mutations. 64 New vectors have been developed and nonviral approaches, such as gene activated matrices, are also promising. 114 …”

Section: Systemic Versus Local Delivery Of Cells For Bone Repairmentioning

confidence: 99%

“…64,87 These cells can all be induced into osteoblasts or chondrocytes in vitro. In the study by Zhang et al, human fetal MSCs (hfMSCs) were shown to augment healing of rat critical-sized defects via stimulating vascularization.…”

Section: Main Cell Sources For Bone Tissue Engineeringmentioning

confidence: 99%

Cell Sources for Bone Tissue Engineering: Insights from Basic Science

Colnot

2011

Tissue Engineering Part B: Reviews

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One of the goals of bone tissue engineering is to design delivery methods for skeletal stem/progenitor cells to repair or replace bone. Although the materials used to retain cells play a central role in the quality of the constructs, the source of cells is key for bone regeneration. Bone marrow is the most common cell source, but other tissues are now being explored, such as the periosteum, fat, muscle, cord blood, and embryonic or induced pluripotent stem cells. The therapeutic effect of exogenous stem/progenitor cells is accepted, yet their contribution to bone repair is not well defined. The in vitro osteo- and/or chondrogenic potential of these skeletal progenitors do not necessarily predict their differentiation potential in vivo and their function may be affected by their ability to home correctly to bone. This review provides an overview of animal models used to test the efficacy of cell-based approaches. We examine the mechanisms of endogenous cell recruitment during bone repair and compare the role of local versus systemic cell recruitment. We discuss how the normal repair process can help define efficacious cell sources for bone tissue engineering and improve their methods of delivery.

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“…plasminogen activator; bone repair; osteoblast; cell proliferation; vessel formation ALTHOUGH AN AUTOGENOUS BONE GRAFT is the gold standard procedure for the reconstruction of a bone defect, it has several disadvantages, including the limited size of the graft and injury to the donor site (23). Fractures are one of the most frequent injuries of the musculoskeletal system.…”

mentioning

confidence: 99%

Tissue-type plasminogen activator deficiency delays bone repair: roles of osteoblastic proliferation and vascular endothelial growth factor

Kawao

Tamura

Okumoto

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Further development in research of bone regeneration is necessary to meet the clinical demand for bone reconstruction. Recently, we reported that plasminogen is crucial for bone repair through enhancement of vessel formation. However, the details of the role of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) in the bone repair process still remain unknown. Herein, we examined the effects of plasminogen activators on bone repair after a femoral bone defect using tPA-deficient ( tPA−/−) and uPA-deficient ( uPA−/−) mice. Bone repair of the femur was delayed in tPA−/− mice, unlike that in wild-type ( tPA+/+) mice. Conversely, the bone repair was comparable between wild-type ( uPA+/+) and uPA−/− mice. The number of proliferative osteoblasts was decreased at the site of bone damage in tPA−/− mice. Moreover, the proliferation of primary calvarial osteoblasts was reduced in tPA−/− mice. Recombinant tPA facilitated the proliferation of mouse osteoblastic MC3T3-E1 cells. The proliferation enhanced by tPA was antagonized by the inhibition of endogenous annexin 2 by siRNA and by the inhibition of extracellular signal-regulated kinase (ERK)1/2 phosphorylation in MC3T3-E1 cells. Vessel formation as well as the levels of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) were decreased at the damaged site in tPA−/− mice. Our results provide novel evidence that tPA is crucial for bone repair through the facilitation of osteoblast proliferation related to annexin 2 and ERK1/2 as well as enhancement of vessel formation related to VEGF and HIF-1α at the site of bone damage.

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Concise Review: Induced Pluripotent Stem Cells and Lineage Reprogramming: Prospects for Bone Regeneration

Cited by 55 publications

References 127 publications

Dental Pulp of the Third Molar: A New Source of Pluripotent-like Stem Cells

Dental Pulp of the Third Molar: A New Source of Pluripotent-like Stem Cells

Cell Sources for Bone Tissue Engineering: Insights from Basic Science

Tissue-type plasminogen activator deficiency delays bone repair: roles of osteoblastic proliferation and vascular endothelial growth factor

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