Formation of cartilage matrix proteins by BMP-transfected murine mesenchymal stem cells encapsulated in a novel class of alginates

Weber, M.; Steinert, Andre F.; Jork, Anette; Dimmler, Arno; Thürmer, F.; Schütze, Norbert; Hendrich, Christian; Zimmermann, U.

doi:10.1016/s0142-9612(01)00329-5

Cited by 84 publications

(62 citation statements)

References 43 publications

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“…Another characteristic of ESCs is their ability to induce teratoma formation in immune-deficient mice, which often consist of various tissues, including bone (23,24). Likewise, adult stem cells such as bone marrow stem cells or mesenchymal stem cells have been reported to have differentiation potentials toward osteogenic tissues when transplanted with biomaterials or scaffolding materials such as alginate, HA, and hydrogel (25)(26)(27). In the present study, we transplanted ESCs mixed with HA/TCP into tooth sockets, and found that the ESCs could differentiate into osteogenic structures without teratoma formation.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic potential of embryonic stem cells in tooth sockets

Kang¹,

Roh²,

Lee³

et al. 2008

Int J Mol Med

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Abstract. Embryonic stem cells (ESCs) are established from blastocysts and give rise to various types of cells and tissues. In the present study, we assessed the osteogenic potential of ESCs using in vitro culture conditions and in vivo differentiation in tooth sockets. An ESC-derived embryoid body (EB) was formed and subsequently induced to an osteogenic lineage. The differentiated EB cells exhibited increased expression of various osteogenic markers as determined by real-time PCR analysis. Likewise, the differentiated EB-derived cells had enhanced alkaline phosphatase activity and calcium accumulation, as determined by cytochemical methods. For in vivo transplantation, mixtures of ESCs and hydroxyapatite/ tricalcium phosphate particles or EBs alone were transplanted into female rat tooth sockets. After 12 weeks, we observed formation of osteogenic structure in the tooth sockets without evidence of teratomas. These data suggest that pluripotent ESCs can serve as an alternative source for the reconstruction of craniofacial structures, as well as for further applications.

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Section: Discussionmentioning

confidence: 99%

Osteogenic potential of embryonic stem cells in tooth sockets

Kang¹,

Roh²,

Lee³

et al. 2008

Int J Mol Med

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“…The healing of full-thickness cartilage was also enhanced by combining BMP-7 and microfracture (13). BMP-2, 4, and 6 promote both transcription of collagen type II mRNA and differentiation of MSCs into chondrocytes (14). BMP-2 with Wnt-3A also enhances MSC chondrogenesis, while Wnt-7A induces dedifferentiation (15).…”

Section: Gfsmentioning

confidence: 99%

Stimulation of Chondrogenic Differentiation of Mesenchymal Stem Cells

Han²,

Kim³

2012

Int J Stem Cells

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The methods for cartilage repair have been studied so far, yet many of them seem to have limitations due to the low regenerative capacity of articular cartilage. Mesenchymal stem cell (MSC) has been suggested as an alternative solution to remedy this challenging problem. MSCs, which have extensive differentiation capacity, can be induced to differentiate into chondrocytes under specific conditions. Particularly, this review focused on the effects of growth factors, cell-to-cell interactions and biomaterials in chondrogenesis of MSCs. Appropriate stimulations through these factors are crucial in differentiation and proliferation of MSCs. However, use of MSCs for cartilage repair has some drawbacks and risks, such as expression of hypertrophy-related genes in MSCs-derived chondrocytes and consequent calcification or cell death. Nevertheless, the clinical application of MSCs is expected in the future with advanced technology.

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“…Alginate has been used effectively to deliver human, murine, and lapine BMDMSC to heal musculoskeletal connective tissues, particularly for the induction of chondrogenic differentiation. 10,26,[28][29][30][31][32] In these studies, cells had been preconditioned via exposure to one or more factors previously demonstrated to induce osteogenic and/or chondrogenic differentiation, for example, dexamethasone, ascorbate-2-phosphate, BMP-2, BMP-9, transforming growth factor b1 (TGF-b1), and/or TGF-b3. The ability of an alginate system to support transduced stem cells and accelerate osteogenic differentiation in suspended, isolated cells in vitro has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Gene‐mediated osteogenic differentiation of stem cells by bone morphogenetic proteins‐2 or ‐6

Zachos

Shields

Bertone

2006

Journal Orthopaedic Research

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Bone marrow-derived mesenchymal stem cells (BMDMSC) hold promise for targeted osteogenic differentiation and can be augmented by delivery of genes encoding bone morphogenetic proteins (BMP). The feasibility of promoting osteogenic differentiation of BMDMSC was investigated using two BMP genes in monolayer and three-dimensional alginate culture systems. Cultured BMDMSC were transduced with E1-deleted adenoviral vectors containing either human BMP2 or BMP6 coding sequence under cytomegalovirus (CMV) promoter control [17:1 multiplicities of infection (moi)] and either sustained in monolayer or suspended in 1 mL 1.2% alginate beads for 22 days. Adenovirus (Ad)-BMP-2 and Ad-BMP-6 transduction resulted in abundant BMP-2 and BMP-6 mRNA and protein expression in monolayer culture and BMP-2 protein expression in alginate cultures. Ad-BMP-2 and Ad-BMP-6 transduced BMDMSC in monolayer had earlier and robust alkaline phosphatase-positive staining and mineralization and were sustained for a longer duration with better morphology scores than untransduced or Ad-b-galactosidase-transduced cells. Ad-BMP-2-and, to a lesser degree, Ad-BMP-6-transduced BMDMSC suspended in alginate demonstrated greater mineralization than untransduced cells. Gene expression studies at day 2 confirmed an inflammatory response to the gene delivery process with upregulation of interleukin 8 and CXCL2. Upregulation of genes consistent with response to BMP exposure and osteogenic differentiation, specifically endochondral ossification and extracellular matrix proteins, occurred in BMP-transduced cells. These data support that transduction of BMDMSC with Ad-BMP-2 or Ad-BMP-6 can accelerate osteogenic differentiation and mineralization of stem cells in culture, including in three-dimensional culture. BMP-2-transduced stem cells suspended in alginate culture may be a practical carrier system to support bone formation in vivo. BMP-6 induced a less robust cellular response than BMP-2, particularly in alginate culture. ß

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Formation of cartilage matrix proteins by BMP-transfected murine mesenchymal stem cells encapsulated in a novel class of alginates

Cited by 84 publications

References 43 publications

Osteogenic potential of embryonic stem cells in tooth sockets

Osteogenic potential of embryonic stem cells in tooth sockets

Stimulation of Chondrogenic Differentiation of Mesenchymal Stem Cells

Gene‐mediated osteogenic differentiation of stem cells by bone morphogenetic proteins‐2 or ‐6

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