Recent studies have shown that mesenchymal stem cell (MSC)-based therapy might be an effective approach for the treatment of intervertebral disc degeneration (IDD). However, many unanswered questions remain before clinical translation, such as the most effective stem cell type, a reliable transplantation method, including the carrier choice, and the fate of stem cells after misdirected delivery, among others. The objective of the study was to evaluate the fate and effect of allogenic bone marrow MSCs after transplantation into an IDD model. The L2-3, L3-4 and L4-5 intervertebral discs (IVDs) of four rabbits were stabbed to create IDD. Rabbit MSCs were expanded in vitro and in part transduced with retrovirus/eGFP. After 3 weeks, 1 × 105 MSCs were injected into the IVDs. The rabbits were followed by X-ray and MRI 3 and 9 weeks after injection. Then the animals were sacrificed and the spines analysed histologically. MRI showed no signs of regeneration. X-ray and gross anatomy inspection demonstrated large anterolateral osteophytes. Histological analysis showed that the osteophytes were composed of mineralized tissue surrounded by chondrocytes, with the labelled MSCs among the osteophyte-forming cells. The labelled MSCs were not found in the nucleus. Inflammatory cells were not observed in any injected IVDs. These results raise concern that MSCs can migrate out of the nucleus and undesirable bone formation may occur. While cause cannot be inferred from this study, the presence of MSCs in the osteophytes suggests a potential side-effect with this approach. IVD regeneration strategies need to focus on cell carrier systems and annulus-sealing technologies to avoid pitfalls. © 2011 John Wiley & Sons, Ltd.

Mesenchymal stem cells injection in degenerated intervertebral disc: Cell leakage may induce osteophyte formation

Vadalà G.
;
Denaro V.;
2012-01-01

Abstract

Recent studies have shown that mesenchymal stem cell (MSC)-based therapy might be an effective approach for the treatment of intervertebral disc degeneration (IDD). However, many unanswered questions remain before clinical translation, such as the most effective stem cell type, a reliable transplantation method, including the carrier choice, and the fate of stem cells after misdirected delivery, among others. The objective of the study was to evaluate the fate and effect of allogenic bone marrow MSCs after transplantation into an IDD model. The L2-3, L3-4 and L4-5 intervertebral discs (IVDs) of four rabbits were stabbed to create IDD. Rabbit MSCs were expanded in vitro and in part transduced with retrovirus/eGFP. After 3 weeks, 1 × 105 MSCs were injected into the IVDs. The rabbits were followed by X-ray and MRI 3 and 9 weeks after injection. Then the animals were sacrificed and the spines analysed histologically. MRI showed no signs of regeneration. X-ray and gross anatomy inspection demonstrated large anterolateral osteophytes. Histological analysis showed that the osteophytes were composed of mineralized tissue surrounded by chondrocytes, with the labelled MSCs among the osteophyte-forming cells. The labelled MSCs were not found in the nucleus. Inflammatory cells were not observed in any injected IVDs. These results raise concern that MSCs can migrate out of the nucleus and undesirable bone formation may occur. While cause cannot be inferred from this study, the presence of MSCs in the osteophytes suggests a potential side-effect with this approach. IVD regeneration strategies need to focus on cell carrier systems and annulus-sealing technologies to avoid pitfalls. © 2011 John Wiley & Sons, Ltd.
Cell therapy
Disc degeneration
Intervertebral disc
Mesenchymal stem cells
Osteophyte
Side-effect
Animals
Female
Intervertebral Disc Degeneration
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells
Osteophyte
Rabbits
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12610/67655
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 95
  • Scopus 221
  • ???jsp.display-item.citation.isi??? ND
social impact