PMID- 30179944
OWN - NLM
STAT- MEDLINE
DCOM- 20190916
LR  - 20220129
IS  - 1528-1132 (Electronic)
IS  - 0009-921X (Print)
IS  - 0009-921X (Linking)
VI  - 476
IP  - 10
DP  - 2018 Oct
TI  - Adipose-derived Human Perivascular Stem Cells May Improve Achilles Tendon Healing 
      in Rats.
PG  - 2091-2100
LID - 10.1097/CORR.0000000000000461 [doi]
AB  - BACKGROUND: Achilles tendon rupture is a common injury and the best treatment 
      option remains uncertain between surgical and nonoperative methods. Biologic 
      approaches using multipotent stem cells such as perivascular stem cells pose a 
      possible treatment option, although there is currently a paucity of evidence 
      regarding their clinical therapeutic use. QUESTIONS/PURPOSES: The purpose of this 
      study was to determine whether injected perivascular stem cells (PSCs) would (1) 
      improve histologic signs of tendon healing (such as percent area of collagen); 
      and (2) improve biomechanical properties (peak load or stiffness) in a rat model 
      of Achilles tendon transection. METHODS: Two subtypes of PSCs were derived from 
      human adipose tissue: pericytes (CD146CD34CD45CD31) and adventitial cells 
      (CD146CD34CD45CD31). Thirty-two athymic rats underwent right Achilles transection 
      and were randomized to receive injection with saline (eight tendons), hydrogel 
      (four tendons), pericytes in hydrogel (four tendons), or adventitial cells in 
      hydrogel (eight tendons) 3 days postoperatively with the left serving as an 
      uninjured control. Additionally, a subset of pericytes was labeled with CM-diI to 
      track cell viability and localization. At 3 weeks, the rats were euthanized, and 
      investigators blinded to treatment group allocation evaluated tendon healing by 
      peak load and stiffness using biomechanical testing and percent area of collagen 
      using histologic analysis with picrosirius red staining. RESULTS: Histologic 
      analysis showed a higher mean percent area collagen for pericytes (30%) and 
      adventitial cells (28%) than hydrogel (21%) or saline (26%). However, a 
      nonparametric statistical analysis yielded no statistical difference. Mechanical 
      testing demonstrated that the pericyte group had a higher peak load than the 
      saline group (41 +/- 7 N versus 26 +/- 9 N; mean difference 15 N; 95% confidence 
      interval [CI], 4-27 N; p = 0.003) and a higher peak load than the hydrogel group 
      (41 +/- 7 N versus 25 +/- 3 N; mean difference 16; 95% CI, 8-24 N; p = 0.001). The 
      pericyte group demonstrated higher stiffness than the hydrogel group (36 +/- 12 
      N/mm versus 17 +/- 6 N/mm; mean difference 19 N/mm; 95% CI, 5-34 N/mm; p = 0.005). 
      CONCLUSIONS: Our results suggest that injection of PSCs improves mechanical but 
      not the histologic properties of early Achilles tendon healing. CLINICAL 
      RELEVANCE: This is a preliminary study that provides more insight into the use of 
      adipose-derived PSCs as a percutaneous therapy in the setting of Achilles tendon 
      rupture. Further experiments to characterize the function of these cells may 
      serve as a pathway to development of minimally invasive intervention aimed at 
      improving nonoperative management while avoiding the complications associated 
      with surgical treatment down the line.
FAU - Devana, Sai K
AU  - Devana SK
AD  - S. K. Devana, B. V. Kelley, O. J. McBride, N. Kabir, A. R. Jensen, S. J. Park, C. 
      D. Eliasberg, A. Dar, G. M. Mosich, T. J. Kowalski, B. Peault, F. A. Petrigliano, 
      N. F. SooHoo, Department of Orthopaedic Surgery, University of California Los 
      Angeles, David Geffen School of Medicine, Los Angeles, CA, USA C. D. Eliasberg, 
      Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, NY, 
      USA T. J. Kowalski, Department of Orthopaedic Surgery, Queen Elizabeth Hospital 
      Birmingham, Birmingham, UK B. Peault, University of Edinburgh, MRC Center for 
      Regenerative Medicine, Edinburgh, UK.
FAU - Kelley, Benjamin V
AU  - Kelley BV
FAU - McBride, Owen J
AU  - McBride OJ
FAU - Kabir, Nima
AU  - Kabir N
FAU - Jensen, Andrew R
AU  - Jensen AR
FAU - Park, Se Jin
AU  - Park SJ
FAU - Eliasberg, Claire D
AU  - Eliasberg CD
FAU - Dar, Ayelet
AU  - Dar A
FAU - Mosich, Gina M
AU  - Mosich GM
FAU - Kowalski, Tomasz J
AU  - Kowalski TJ
FAU - Peault, Bruno
AU  - Peault B
FAU - Petrigliano, Frank A
AU  - Petrigliano FA
FAU - SooHoo, Nelson F
AU  - SooHoo NF
LA  - eng
GR  - G1000816/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PL  - United States
TA  - Clin Orthop Relat Res
JT  - Clinical orthopaedics and related research
JID - 0075674
RN  - 0 (Biomarkers)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Achilles Tendon/metabolism/physiopathology/*surgery
MH  - Adipose Tissue/*cytology
MH  - Adventitia/*cytology
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Biomechanical Phenomena
MH  - Cells, Cultured
MH  - Collagen/metabolism
MH  - Disease Models, Animal
MH  - Humans
MH  - Male
MH  - Multipotent Stem Cells/metabolism/*transplantation
MH  - Pericytes/metabolism/*transplantation
MH  - Phenotype
MH  - Rats, Nude
MH  - *Stem Cell Transplantation
MH  - Tendon Injuries/metabolism/physiopathology/*surgery
MH  - Time Factors
MH  - *Wound Healing
PMC - PMC6259872
COIS- All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and 
      Related Research(R) editors and board members are on file with the publication and 
      can be viewed on request.
EDAT- 2018/09/05 06:00
MHDA- 2019/09/17 06:00
PMCR- 2019/10/01
CRDT- 2018/09/05 06:00
PHST- 2018/09/05 06:00 [pubmed]
PHST- 2019/09/17 06:00 [medline]
PHST- 2018/09/05 06:00 [entrez]
PHST- 2019/10/01 00:00 [pmc-release]
AID - CORR-D-17-01764 [pii]
AID - 10.1097/CORR.0000000000000461 [doi]
PST - ppublish
SO  - Clin Orthop Relat Res. 2018 Oct;476(10):2091-2100. doi: 
      10.1097/CORR.0000000000000461.