Intraoperative Stem Cell Therapy

Coelho, Mónica B.; Cabral, Joaquim M. S.; Karp, Jeffrey M.

doi:10.1146/annurev-bioeng-071811-150041

Cited by 47 publications

(40 citation statements)

References 114 publications

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“…4,5 In order to address this primary obstacle, intraoperative stem cell therapy strategies have been developed that include the selection and concentration of autologous progenitor cells by minimal processing within the operating room and their immediate re-implantation to patients at the time of care. 6 …”

Section: Introductionmentioning

confidence: 99%

Cell-Mediated Dexamethasone Release from Semi-IPNs Stimulates Osteogenic Differentiation of Encapsulated Mesenchymal Stem Cells

Bae

Lee

et al. 2015

Biomacromolecules

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Scaffold-based delivery of bioactive molecules capable of directing stem cell differentiation is critical to the development of point-of-care cell therapy for orthopaedic repair. Dexamethasone-conjugated hyaluronic acid (HA-DXM) was synthesized and combined with hydrolytically degradable, photocrosslinkable PEG-bis-(2-acryloyloxy propanoate) (PEG-bis-AP) to form semi-IPNs. Dexamethasone (DX) release was limited in physiological buffer and substantially increased in the presence of encapsulated human mesenchymal stem cells (hMSCs) or exogenous hyaluronidase, confirming that release occurred primarily by a cell-mediated enzymatic mechanism. hMSCs encapsulated in PEG-bis-AP/HA-DXM semi-IPNs increased osteoblast-specific gene expression, alkaline phosphatase activity, and matrix mineralization, attaining levels that were not significantly different from positive controls consisting of hMSCs in PEG-bis-AP/native HA cultured with DX supplementation in the culture medium. These studies demonstrate that PEG-bis-AP/HA-DXM semi-IPNs can provide cell-mediated release of bioactive free DX that induces hMSC osteogenic differentiation. This approach offers an efficient system for local delivery of osteogenic molecules empowering point of care applications.

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Section: Introductionmentioning

confidence: 99%

Cell-Mediated Dexamethasone Release from Semi-IPNs Stimulates Osteogenic Differentiation of Encapsulated Mesenchymal Stem Cells

Bae

Lee

et al. 2015

Biomacromolecules

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“…The absence of a unique surface marker for the separation of all MSCs makes it a challenge to choose the right surface marker or marker combinations with regard to MSC yield versus MSC purity (Coelho et al, ). The present study has shown that CD271 is a suitable separation marker to isolate MSCs.…”

Section: Discussionmentioning

confidence: 99%

“…Novel PoC approaches for cartilage treatment have focused on obtaining a highly clonogenic, proliferative, and potent chondrogenic MSC subpopulation by either removing undesired cell populations or by positive selection of target cells based on surface markers (Coelho, Cabral, Joaquim, & Karp, 2012;Roelofs et al, 2013). However, due to the current lack of a unique surface marker for MSCs, a number of surface molecules have been suggested for prospective isolation of MSCs (Calloni, Cordero, Henriques, & Bonatto, 2013).…”

Section: Introductionmentioning

confidence: 99%

Point-of-care treatment of focal cartilage defects with selected chondrogenic mesenchymal stromal cells-An in vitro proof-of-concept study

Petters

Schmidt

Thuemmler

et al. 2018

J Tissue Eng Regen Med

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Due to the poor self-healing capacities of cartilage, innovative approaches are a major clinical need. The use of in vitro expanded mesenchymal stromal cells (MSCs) in a 2-stage approach is accompanied by cost-, time-, and personnel-intensive good manufacturing practice production. A 1-stage intraoperative procedure could overcome these drawbacks. The aim was to prove the feasibility of a point-of-care concept for the treatment of cartilage lesions using defined MSC subpopulations in a collagen hydrogel without prior MSC monolayer expansion. We tested 4 single marker candidates (MSCA-1, W4A5, CD146, CD271) for their effectiveness of separating colony-forming units of ovine MSCs via magnetic cell separation. The most promising surface marker with regard to the highest enrichment of colony-forming cells was subsequently used to isolate a MSC subpopulation for the direct generation of a cartilage graft composed of a collagen type I hydrogel without the propagation of MSCs in monolayer. We observed that separation with CD271 sustained the highest enrichment of colony-forming units. We then demonstrated the feasibility of generating a cartilage graft with an unsorted bone marrow mononuclear cell fraction and with a characterized CD271 positive MSC subpopulation without the need for a prior cell expansion. A reduced volume of 6.25% of the CD271 positive MSCs was needed to achieve the same results regarding chondrogenesis compared with the unseparated bone marrow mononuclear cell fraction, drastically reducing the number of nonrelevant cells. This study provides a proof-of-concept and reflects the potential of an intraoperative procedure for direct seeding of cartilage grafts with selected CD271 positive cells from bone marrow.

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“…(POC) biologics amenable to single step interventions appear attractive and may provide an alternative and viable strategy (38).…”

Section: Discussionmentioning

confidence: 99%

Chondrocyte-based intraoperative processing strategies for the biological augmentation of a polyurethane meniscus replacement

Vedicherla

Romanazzo

Kelly

et al. 2017

Connective Tissue Research

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Purpose/Aim of Study: Menisectomies account for over 1.5 million surgical interventions in Europe annually and there is a growing interest in regenerative strategies to improve outcomes in meniscal replacement. The overall objective of this study was to evaluate the role of intraoperatively applied fresh chondrocyte isolates compared to minced cartilage fragments, used without cell isolation, to improve bioactivity and tissue integration when combined with a polyurethane replacement. Materials and Methods:Firstly, to optimise the intraoperative cell isolation protocol, caprine articular cartilage biopsies were digested with 750 U/ml or 3000 U/ml collagenase type II (ratio of 10 ml per g of tissue) for 30 min, 1 h or 12 hrs with constant agitation and compared to culture expanded chondrocytes in terms of matrix deposition when cultured on polyurethane scaffolds. Finally, fresh chondrocytes and minced cartilage augmented polyurethane scaffolds were evaluated in a caprine meniscal explant model to assess the potential enhancements on tissue integration strength.Results: Adequate numbers of fresh chondrocytes were harvested using a 30 min chondrocyte isolation protocol and demonstrated improved matrix deposition compared to standard culture expanded cells in vitro. Upon evaluation in a meniscus explant defect model, both fresh chondrocytes and minced cartilage showed improved matrix deposition at the tissue scaffold interface and enhanced push-out strength, 4 fold and 2.5 fold respectively compared with the acellular implant. Conclusions:Herein, we have demonstrated a novel approach that could be applied intraoperatively using fresh chondrocytes or minced cartilage for improved tissue integration with a polyurethane meniscal replacement.

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Intraoperative Stem Cell Therapy

Cited by 47 publications

References 114 publications

Cell-Mediated Dexamethasone Release from Semi-IPNs Stimulates Osteogenic Differentiation of Encapsulated Mesenchymal Stem Cells

Cell-Mediated Dexamethasone Release from Semi-IPNs Stimulates Osteogenic Differentiation of Encapsulated Mesenchymal Stem Cells

Point-of-care treatment of focal cartilage defects with selected chondrogenic mesenchymal stromal cells-An in vitro proof-of-concept study

Chondrocyte-based intraoperative processing strategies for the biological augmentation of a polyurethane meniscus replacement

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