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Human stem cell delivery for treatment of large segmental bone defects.

ABSTRACT: Local or systemic stem cell delivery has the potential to promote repair of a variety of damaged or degenerated tissues. Although various stem cell sources have been investigated for bone repair, few comparative reports exist, and cellular distribution and viability postimplantation remain key issues. In this study, we quantified the ability of tissue-engineered constructs containing either human fetal or adult stem cells to enhance functional repair of nude rat critically sized femoral defects. After 12 weeks, defects treated with cell-seeded polymer scaffolds had significantly higher bone ingrowth and torsional strength compared to those receiving acellular scaffolds, although there were no significant differences between the cell sources. Next, stem cells were labeled with fluorescent quantum dots (QDs) in an attempt to noninvasively track their distribution after delivery on scaffolds. Clear fluorescence was observed at implantation sites throughout the study; however, beginning 7-10 days after surgery, signals were also observed at contralateral sites treated with acellular QD-free scaffolds. Although immunostaining for human nuclei revealed retention of some cells at the implantation site, no human cells were detected in the control limb defects. Additional histological analysis of implantation and control defect tissues revealed macrophages containing endocytosed QDs. Furthermore, QD-labeling appeared to diminish transplanted cell function resulting in reduced healing responses. In summary, augmentation of polymeric scaffolds with stem cells derived from fetal and adult tissues significantly enhanced healing of large segmental bone defects; however, QD labeling of stem cells eliminated the observed therapeutic effect and failed to conclusively track stem cell location long-term in vivo.

SUBMITTER: Dupont KM

PROVIDER: S-EPMC2840521 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Human stem cell delivery for treatment of large segmental bone defects.

Dupont Kenneth M KM Sharma Kapil K Stevens Hazel Y HY Boerckel Joel D JD García Andrés J AJ Guldberg Robert E RE

Proceedings of the National Academy of Sciences of the United States of America 20100119 8

Local or systemic stem cell delivery has the potential to promote repair of a variety of damaged or degenerated tissues. Although various stem cell sources have been investigated for bone repair, few comparative reports exist, and cellular distribution and viability postimplantation remain key issues. In this study, we quantified the ability of tissue-engineered constructs containing either human fetal or adult stem cells to enhance functional repair of nude rat critically sized femoral defects. ...[more]

PMID: 20133731

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Project description:BackgroundBone tissue engineering is not widely used in clinical treatment. Two main reasons hide behind this: (1) the seed cells are difficult to obtain and (2) the process of tissue engineering bone construction is too complex and its efficiency is still relatively low. It is foreseeable that in the near future, the problem of seed cell sources could be solved completely in tissue engineering bone repair. As for the complex process and low efficiency of tissue engineering bone construction, usually two strategies would be considered: (1) the construction strategy based on injectable bone tissue and (2) the construction strategy based on osteogenic cell sheets. However, the application of injectable bone tissue engineering (iBTE) strategy and osteogenic cell sheet strategy is limited and they could hardly be used directly in repairing defects of large segmental bone, especially load-bearing bone.MethodsIn this study, we built an osteogenic micro-tissue with simple construction but with a certain structure and composition. Based on this, we established a new iBTE repair strategy-osteogenic micro-tissue in situ repair strategy, mainly targeting at solving the problem of large segmental bone defect. The steps are as follows: (1) Build the biodegradable three-dimensional scaffold based on the size of the defect site with 3D printing rapid prototyping technology. (2) Implant the three-dimensional scaffold into the defect site. This scaffold is considered as the "steel framework" that could provide both mechanical support and space for bone tissue growth. (3) Inject the osteogenic micro-tissue (i.e., the "cell-extracellular matrix" complex), which could be considered as "concrete," into the three-dimensional scaffold, to promote the bone tissue regeneration in situ. Meanwhile, the digested cells were injected as the compared group in this experiment. After 3 months, the effect of in situ bone defect repair of osteogenic micro-tissue and digested cells was compared.ResultsIt is confirmed that osteogenic micro-tissue could achieve a higher efficiency on cell usage and has a better repair effect than the digested cells.ConclusionsOsteogenic micro-tissue repairing strategy would be a more promising clinical strategy to solve the problem of large segmental bone defect.

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Human stem cell delivery for treatment of large segmental bone defects.

Publications

Human stem cell delivery for treatment of large segmental bone defects.

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