Sains Malaysiana 53(1)(2024): 63-86

http://doi.org/10.17576/jsm-2024-5301-06

Genetically Engineered Mesenchymal Stem Cells using Viral Vectors: A New Frontier in Anti-Angiogenic Therapy

(Sel Stem Mesenkima Kejuruteraan Genetik menggunakan Vektor Virus: Suatu Sempadan Baharu dalam Terapi Anti-Angiogenik)

EWA CHOY YEE WA^1,*, CHOY KER WOON^2,3, WOON KAI SIONG¹, MUHAMMAD AIDIL WAFI¹, THEN KONG YONG¹ & THEN KHONG LEK¹

¹CryoCord Sdn. Bhd., Suite 1-1, 1st Floor, Bio X Centre, Persiaran Cyberpoint Selatan, Cyber 8, 63000

Cyberjaya, Selangor, Malaysia

²Department of Anatomy, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh

Campus,Jalan Hospital, 47000 UiTM Sungai Buloh, Selangor, Malaysia

³Institute of Pathology, Laboratory and Forensic Medicine (I-PPerForM),

Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Malaysia.

Diserahkan: 26 Jun 2023/Diterima: 9 Januari 2024

Abstract

Mesenchymal stem cells (MSCs) are adult stem cells that possess the remarkable ability to self-renew and differentiate into various cell lineages. Due to their regenerative potential, MSCs have emerged as the most commonly used stem cell type in clinical applications. Angiogenesis, the formation of new blood vessels, plays a critical role in several pathological conditions, including ocular neovascular diseases, cancer, and inflammatory disorders. Conventional anti-angiogenic therapies face limitations such as frequent visits for repeated doses, off-target effects and resistance development. Recent advances in genetic engineering techniques have opened up novel avenues in regenerative medicine. Genetically engineering MSCs using viral vectors presents a promising strategy to specifically target angiogenesis and enhance anti-angiogenic therapies' efficacy. Viral vectors, including lentiviruses, adeno-associated viruses and adenoviruses, provide an effective means of delivering therapeutic genes into MSCs, allowing the expression of a wide range of therapeutic agents, including anti-angiogenic proteins. This review explores the frontier of using genetically engineered MSCs delivered through viral vectors as a potent anti-angiogenic therapeutic approach. By leveraging the unique properties of MSCs and the targeted delivery capabilities of viral vectors, this approach initiates the potential to revolutionize anti-angiogenic therapy, offering new possibilities for the treatment of angiogenesis-related diseases.

Keywords: Angiogenesis; anti-angiogenic therapy; genetic engineering; mesenchymal stem cells; viral vectors

Abstrak

Sel stem mesenkima (MSCs) adalah sel stem dewasa yang memiliki keupayaan luar biasa untuk memperbaharui diri dan berubah menjadi pelbagai barisan sel. Disebabkan potensi regeneratif mereka, MSCs telah menjadi jenis sel stem yang paling biasa digunakan dalam aplikasi klinikal. Angiogenesis, pembentukan saluran darah baru, memainkan peranan penting dalam beberapa keadaan patologi, termasuk penyakit neovaskular okular, kanser dan penyakit keradangan. Terapi anti-angiogenesis konvensional mempunyai kekurangan seperti lawatan kerap untuk dos berulang, kesan di luar sampingan dan pembangunan rintangan. Kemajuan terkini dalam teknik kejuruteraan genetik telah membuka peluang baharu dalam perubatan regeneratif. Kejuruteraan genetik MSCs menggunakan vektor virus merupakan strategi yang berpotensi untuk menyerang angiogenesis secara khusus dan meningkatkan keberkesanan terapi anti-angiogenesis. Vektor virus termasuk lentivirus, virus adeno-terkait dan adenovirus menyediakan cara yang berkesan untuk menghantar gen terapi ke dalam MSCs, membolehkan ekspresi pelbagai agen terapeutik, termasuk protein anti-angiogenesis. Kajian ini meneroka hala tuju penggunaan MSCs yang direka bentuk secara genetik yang dihantar melalui vektor virus sebagai pendekatan terapeutik anti-angiogenesis yang berkuasa. Dengan memanfaatkan sifat unik MSCs dan keupayaan penghantaran yang dituju oleh vektor virus, pendekatan ini berpotensi untuk mengubah terapi anti-angiogenesis, menawarkan kemungkinan baru untuk rawatan penyakit berkaitan angiogenesis.

Kata kunci: Angiogenesis; kejuruteraan genetik; sel stem mesenkima; terapi anti-angiogenesis; vektor virus

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