Adipose-derived Human Perivascular Stem Cells May Improve Achilles Tendon Healing in Rats

Sai K. Devana; Benjamin V. Kelley; Owen J. McBride; Nima Kabir; Andrew R. Jensen; Se Jin Park; Claire D. Eliasberg; Ayelet Dar; Gina M. Mosich; Tomasz J. Kowalski; Bruno Peault; Frank A. Petrigliano; Nelson F. SooHoo

doi:10.1097/CORR.0000000000000461

Adipose-derived Human Perivascular Stem Cells May Improve Achilles Tendon Healing in Rats

Sai K. Devana^*, Benjamin V. Kelley, Owen J. McBride, Nima Kabir, Andrew R. Jensen, Se Jin Park, Claire D. Eliasberg, Ayelet Dar, Gina M. Mosich, Tomasz J. Kowalski, Bruno Peault, Frank A. Petrigliano, Nelson F. SooHoo

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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 (CD146(+) CD34(-)CD45(-)CD31(-)) and adventitial cells (CD146(-)CD34(+)CD45(-)CD31(-)). 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.

Original language	English
Pages (from-to)	2091-2100
Number of pages	10
Journal	Clinical Orthopaedics and Related Research
Volume	476
Issue number	10
DOIs	https://doi.org/10.1097/CORR.0000000000000461
Publication status	Published - Oct 2018

Keywords / Materials (for Non-textual outputs)

BONE-MARROW
TISSUE
PERICYTES
RUPTURE
TRANSPLANTATION
ORIGIN

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10.1097/CORR.0000000000000461

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Devana, S. K., Kelley, B. V., McBride, O. J., Kabir, N., Jensen, A. R., Park, S. J., Eliasberg, C. D., Dar, A., Mosich, G. M., Kowalski, T. J., Peault, B., Petrigliano, F. A., & SooHoo, N. F. (2018). Adipose-derived Human Perivascular Stem Cells May Improve Achilles Tendon Healing in Rats. Clinical Orthopaedics and Related Research, 476(10), 2091-2100. https://doi.org/10.1097/CORR.0000000000000461

@article{05ff032c189e4740a993e8ac37708be5,

title = "Adipose-derived Human Perivascular Stem Cells May Improve Achilles Tendon Healing in Rats",

abstract = "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 (CD146(+) CD34(-)CD45(-)CD31(-)) and adventitial cells (CD146(-)CD34(+)CD45(-)CD31(-)). 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.",

keywords = "BONE-MARROW, TISSUE, PERICYTES, RUPTURE, TRANSPLANTATION, ORIGIN",

author = "Devana, {Sai K.} and Kelley, {Benjamin V.} and McBride, {Owen J.} and Nima Kabir and Jensen, {Andrew R.} and Park, {Se Jin} and Eliasberg, {Claire D.} and Ayelet Dar and Mosich, {Gina M.} and Kowalski, {Tomasz J.} and Bruno Peault and Petrigliano, {Frank A.} and SooHoo, {Nelson F.}",

year = "2018",

month = oct,

doi = "10.1097/CORR.0000000000000461",

language = "English",

volume = "476",

pages = "2091--2100",

journal = "Clinical Orthopaedics and Related Research",

issn = "0009-921X",

publisher = "Lippincott Williams & Wilkins",

number = "10",

}

Devana, SK, Kelley, BV, McBride, OJ, Kabir, N, Jensen, AR, Park, SJ, Eliasberg, CD, Dar, A, Mosich, GM, Kowalski, TJ, Peault, B, Petrigliano, FA & SooHoo, NF 2018, 'Adipose-derived Human Perivascular Stem Cells May Improve Achilles Tendon Healing in Rats', Clinical Orthopaedics and Related Research, vol. 476, no. 10, pp. 2091-2100. https://doi.org/10.1097/CORR.0000000000000461

TY - JOUR

T1 - Adipose-derived Human Perivascular Stem Cells May Improve Achilles Tendon Healing in Rats

AU - Devana, Sai K.

AU - Kelley, Benjamin V.

AU - McBride, Owen J.

AU - Kabir, Nima

AU - Jensen, Andrew R.

AU - Park, Se Jin

AU - Eliasberg, Claire D.

AU - Dar, Ayelet

AU - Mosich, Gina M.

AU - Kowalski, Tomasz J.

AU - Peault, Bruno

AU - Petrigliano, Frank A.

AU - SooHoo, Nelson F.

PY - 2018/10

Y1 - 2018/10

N2 - 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 (CD146(+) CD34(-)CD45(-)CD31(-)) and adventitial cells (CD146(-)CD34(+)CD45(-)CD31(-)). 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.

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 (CD146(+) CD34(-)CD45(-)CD31(-)) and adventitial cells (CD146(-)CD34(+)CD45(-)CD31(-)). 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.

KW - BONE-MARROW

KW - TISSUE

KW - PERICYTES

KW - RUPTURE

KW - TRANSPLANTATION

KW - ORIGIN

U2 - 10.1097/CORR.0000000000000461

DO - 10.1097/CORR.0000000000000461

M3 - Article

SN - 0009-921X

VL - 476

SP - 2091

EP - 2100

JO - Clinical Orthopaedics and Related Research

JF - Clinical Orthopaedics and Related Research

IS - 10

ER -

Adipose-derived Human Perivascular Stem Cells May Improve Achilles Tendon Healing in Rats

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