Histological Evidence for Therapeutic Induction of Angiogenesis Using Mast Cells and Platelet-Rich Plasma within A Bioengineered Scaffold following Rat Hindlimb Ischemia


Ali Karimi, Ph.D, 1Rasoul Shahrooz, D.V.Sc, 1,*Rahim Hobbenagh, D.V.Sc, 2Rahim Mohammadi, D.V.Sc, 3Nowruz Delirezh, Ph.D., 2Saeede Amani, Ph.D., 1Johan Garssen, Ph.D., 4,5Esmaeil Mortaz, Ph.D., 4,6,7,*Ian M Adcock, Ph.D., 8,9
Department of Basic Science, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
Department of Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
Department of Surgery and Diagnostic Imaging, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
Nutricia Research Centre for Specialized Nutrition, Utrecht, Netherlands
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Clinical Tuberculosis and Epidemiology Research Center, National Research Institute for Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
Cell and Molecular Biology Group, Airways Disease Section, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom
Priority Research Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
Department of Basic Science, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
Department of Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
Department of Surgery and Diagnostic Imaging, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
Nutricia Research Centre for Specialized Nutrition, Utrecht, Netherlands
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Clinical Tuberculosis and Epidemiology Research Center, National Research Institute for Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
Cell and Molecular Biology Group, Airways Disease Section, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom
Priority Research Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
* Corresponding Addresses: P.O.Box: 57153-1177 Department of Basic Science Faculty of Veterinary Medicine Urmia University Urmia Iran P.O.Box: 19575154 Clinical Tuberculosis and Epidemiology Research Center National Research Institute for Tuberculosis and Lung Disease (NRITLD) Shahid Beheshti University of Medical Sciences Tehran Iran Emails:r.shahrooze@urmia.ac.ir,emortaz@gmail.com
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Karimi Ali, Shahrooz Rasoul, Hobbenagh Rahim, Mohammadi Rahim, Delirezh Nowruz, Amani Saeede, Garssen Johan, Mortaz Esmaeil, M Adcock Ian. Histological Evidence for Therapeutic Induction of Angiogenesis Using Mast Cells and Platelet-Rich Plasma within A Bioengineered Scaffold following Rat Hindlimb Ischemia . Cell J. 2020; 21(4): 391-400.

Abstract

Objective

Peripheral arterial disease results from obstructed blood flow in arteries and increases the risk of amputation in acute cases. Therapeutic angiogenesis using bioengineered tissues composed of a chitosan scaffold that was enriched with mast cells (MCs) and/or platelet-rich plasma (PRP) was used to assess the formation of vascular networks and subsequently improved the functional recovery following hindlimb ischemia. This study aimed to find an optimal approach for restoring local vascularization.

Materials and Methods

In this experimental study, thirty rats were randomly divided into six experimental groups: a. Ischemic control group with right femoral artery transection, b. Ischemia with phosphate-buffered saline (PBS) control group, c. Ischemia with chitosan scaffold, d. Ischemia with chitosan and MCs, e. Ischemia with chitosan and PRP, and f. Ischemia with chitosan, PRP, and MCs. The left hind limbs served as non-ischemic controls. The analysis of capillary density, arterial diameter, histomorphometric analysis and immunohistochemistry at the transected locations and in gastrocnemius muscles was performed.

Results

The group treated with chitosan/MC significantly increased capillary density and the mean number of large blood vessels at the site of femoral artery transection compared with other experimental groups (P<0.05). The treatment with chitosan/MC also significantly increased the muscle fiber diameter and the capillary-to-muscle fiber ratio in gastrocnemius muscles compared with all other ischemic groups (P<0.05).

Conclusion

These findings suggested that chitosan and MCs together could offer a new approach for the therapeutic induction of angiogenesis in cases of peripheral arterial diseases.