PMID- 20808236
OWN - NLM
STAT- MEDLINE
DCOM- 20110602
LR  - 20211020
IS  - 1536-0210 (Electronic)
IS  - 0020-9996 (Print)
IS  - 0020-9996 (Linking)
VI  - 45
IP  - 10
DP  - 2010 Oct
TI  - MR signal characteristics of viable and apoptotic human mesenchymal stem cells in 
      matrix-associated stem cell implants for treatment of osteoarthritis.
PG  - 634-40
LID - 10.1097/RLI.0b013e3181ed566c [doi]
AB  - OBJECTIVE: To compare magnetic resonance (MR) signal characteristics of contrast 
      agent-labeled apoptotic and viable human mesenchymal stem cells (hMSCs) in 
      matrix-associated stem cell implants. METHODS: hMSCs were labeled with Food and 
      Drug Administration-approved ferumoxides nanoparticles. One group (A) remained 
      untreated whereas a second group (B) underwent mitomycin C-induced apoptosis 
      induction. Viability of group A and apoptosis of group B was confirmed by 
      caspase-assays and terminal dUTP nick-end labeling (TUNEL) stains. Labeled viable 
      hMSCs, unlabeled viable hMSCs, labeled apoptotic hMSCs, and unlabeled apoptotic 
      hMSCs (n = 7 samples each) in an agarose scaffold were implanted into cartilage 
      defects of porcine patellae specimens and underwent MR imaging at 7 T, using 
      T1-weighted spin-echo sequences, T2-weighted spin-echo sequences, and 
      T2*-weighted gradient-echo sequences. Signal-to-noise ratios (SNR) of the 
      implants were calculated and compared between different experimental groups using 
      linear mixed regression models. RESULTS: Ferumoxides-labeled hMSCs provided a 
      strong negative T2 and T2*-enhancement. Corresponding SNR data of labeled hMSCs 
      were significantly lower compared with unlabeled controls (P < 0.05). Apoptosis 
      induction resulted in a significant signal decline of ferumoxides-labeled hMSC 
      transplants on short echo time T2-weighted spinecho sequences. SNR data of 
      labeled apoptotic hMSCs were significantly lower compared with labeled viable 
      hMSCs (P < 0.05). CONCLUSION: Apoptosis of transplanted ferumoxides-labeled stem 
      cells in cartilage defects can be visualized noninvasively by a significant 
      signal decline on T2-weighted MR images. The described MR signal characteristics 
      may serve as a noninvasive outcome measure for the assessment of 
      matrix-associated stem cell implants in clinical practice. Additional studies are 
      needed to further enhance the observed differences between viable and apoptotic 
      cells, for example, by further optimizing the applied MR pulse sequence 
      parameters or intracellular contrast agent concentration.
FAU - Nedopil, Alexander
AU  - Nedopil A
AD  - Department of Radiology and Biomedical Imaging, UCSF Medical Center, University 
      of California, San Francisco, CA 94143, USA.
FAU - Klenk, Christopher
AU  - Klenk C
FAU - Kim, Cy
AU  - Kim C
FAU - Liu, Siyuan
AU  - Liu S
FAU - Wendland, Mike
AU  - Wendland M
FAU - Golovko, Daniel
AU  - Golovko D
FAU - Schuster, Tibor
AU  - Schuster T
FAU - Sennino, Barbara
AU  - Sennino B
FAU - McDonald, Donald M
AU  - McDonald DM
FAU - Daldrup-Link, Heike E
AU  - Daldrup-Link HE
LA  - eng
GR  - P01 HL024136/HL/NHLBI NIH HHS/United States
GR  - R01 CA082923/CA/NCI NIH HHS/United States
GR  - HL59157/HL/NHLBI NIH HHS/United States
GR  - R01 HL059157/HL/NHLBI NIH HHS/United States
GR  - CA82923/CA/NCI NIH HHS/United States
GR  - HL24136/HL/NHLBI NIH HHS/United States
GR  - R01AR054458/AR/NIAMS NIH HHS/United States
GR  - R01 AR054458/AR/NIAMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Invest Radiol
JT  - Investigative radiology
JID - 0045377
RN  - 0 (Contrast Media)
RN  - 0 (Dextrans)
RN  - 0 (Ferric Compounds)
RN  - 0 (Magnetite Nanoparticles)
RN  - 1K09F3G675 (ferric oxide)
RN  - 50SG953SK6 (Mitomycin)
RN  - G6N3J05W84 (ferumoxides)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Cartilage Diseases/diagnostic imaging
MH  - Chondrocytes
MH  - Confidence Intervals
MH  - *Contrast Media
MH  - Dextrans
MH  - Ferric Compounds
MH  - *Magnetic Resonance Imaging
MH  - Magnetic Resonance Spectroscopy
MH  - Magnetite Nanoparticles
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Microscopy, Confocal
MH  - Mitomycin
MH  - Nanoparticles
MH  - Osteoarthritis/*therapy
MH  - Radionuclide Imaging
MH  - Swine
PMC - PMC2943569
MID - NIHMS229485
EDAT- 2010/09/03 06:00
MHDA- 2011/06/03 06:00
PMCR- 2011/10/01
CRDT- 2010/09/03 06:00
PHST- 2010/09/03 06:00 [entrez]
PHST- 2010/09/03 06:00 [pubmed]
PHST- 2011/06/03 06:00 [medline]
PHST- 2011/10/01 00:00 [pmc-release]
AID - 10.1097/RLI.0b013e3181ed566c [doi]
PST - ppublish
SO  - Invest Radiol. 2010 Oct;45(10):634-40. doi: 10.1097/RLI.0b013e3181ed566c.