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Tracking mesenchymal stem cell contributions to regeneration in an immunocompetent cartilage regeneration model
Daniela Zwolanek, … , Thomas Rülicke, Reinhold G. Erben
Daniela Zwolanek, … , Thomas Rülicke, Reinhold G. Erben
Published October 19, 2017
Citation Information: JCI Insight. 2017;2(20):e87322. https://doi.org/10.1172/jci.insight.87322.
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Resource and Technical Advance Stem cells Transplantation

Tracking mesenchymal stem cell contributions to regeneration in an immunocompetent cartilage regeneration model

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Abstract

It is currently controversially discussed whether mesenchymal stem cells (MSC) facilitate cartilage regeneration in vivo by a progenitor- or a nonprogenitor-mediated mechanism. Here, we describe a potentially novel unbiased in vivo cell tracking system based on transgenic donor and corresponding immunocompetent marker–tolerant recipient mouse and rat lines in inbred genetic backgrounds. Tolerance of recipients was achieved by transgenic expression of an immunologically neutral but physicochemically distinguishable variant of the marker human placental alkaline phosphatase (ALPP). In this dual transgenic system, donor lines ubiquitously express WT, heat-resistant ALPP protein, whereas recipient lines express a heat-labile ALPP mutant (ALPPE451G) resulting from a single amino acid substitution. Tolerance of recipient lines to ALPP-expressing cells and tissues was verified by skin transplantation. Using this model, we show that intraarticularly injected MSC contribute to regeneration of articular cartilage in full-thickness cartilage defects mainly via a nonprogenitor-mediated mechanism.

Authors

Daniela Zwolanek, María Satué, Verena Proell, José R. Godoy, Kathrin I. Odörfer, Magdalena Flicker, Sigrid C. Hoffmann, Thomas Rülicke, Reinhold G. Erben

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Figure 4

Intraarticularly injected MSC contribute to long-term cartilage regeneration mainly by a nonprogenitor-mediated mechanism.

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Intraarticularly injected MSC contribute to long-term cartilage regenera...
(A) Toluidine blue staining of cryosections from full-thickness cartilage defects 6 months after injection of 1 × 107 MSC from Tg(ALPP) donor rats into WT or Tg(ALPPm) recipients. Black arrow shows neocartilage formation within the defect of Tg(ALPPm) animals. Scale bar: 50 μm. n = 5 per group. (B) Quantification of newly formed cartilage at the defect site, measured with ImageJ. n = 5 per group. *P < 0.05 by Student’s t test. (C–E) Immunofluorescence staining of cryosections from full-thickness cartilage defects, using anti–collagen II (anti-COL2, green) and anti-ALPP antibodies (red) (C), anti-ALPP (green) and anti-SOX9 antibodies (red) (D), or anti-COMP (green) and anti-ALPP antibodies (red) (E) 6 months after injection of 1 × 107 MSC from Tg(ALPP) donor rats into WT or Tg(ALPPm) recipients. White arrows in inset show COL2-containing cartilaginous matrix (C), as well as SOX9 (D) and COMP (E) expression in the newly formed cartilage in Tg(ALPPm) recipients. No ALPP-expressing cells were found in Tg(ALPPm) and WT recipients. Scale bar: 50 μm. n = 5 per group. ALPP, human placental alkaline phosphatase; ALPPm, ALPPE451G mutant; ALPP → ALPPm, transplantation from Tg(ALPP) donor into Tg(ALPPm) recipient.

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

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