Oral delivery of novel human IGF-1 bioencapsulated in lettuce cells promotes musculoskeletal cell proliferation, differentiation and diabetic fracture healing

Autor: S. Yang, J. Park, Henry Daniell, Patricia A. Gonnella, Ming-Lin Liu, G. Yan, Kwang-Chul Kwon
Rok vydání: 2019
Předmět:
Bioencapsulation in plant cells
Biophysics
Administration
Oral
Bioengineering
02 engineering and technology
Bone healing
Pharmacology
Chloroplast
Article
Diabetes Mellitus
Experimental
Biomaterials
03 medical and health sciences
Fractures
Bone
Mice
Downregulation and upregulation
medicine
Animals
Humans
Insulin-Like Growth Factor I
Bone regeneration
Cells
Cultured
030304 developmental biology
Cell Proliferation
Fracture Healing
0303 health sciences
Osteoblasts
business.industry
Cell growth
Regeneration (biology)
Musculoskeletal diseases
Mesenchymal stem cell
Human growth hormones
Osteoblast
Cell Differentiation
Lettuce
021001 nanoscience & nanotechnology
RUNX2
medicine.anatomical_structure
Mechanics of Materials
Ceramics and Composites
Oral biopharmaceutical delivery
0210 nano-technology
business
Zdroj: Biomaterials
ISSN: 1878-5905
Popis: Human insulin-like growth factor-1 (IGF-1) plays important roles in development and regeneration of skeletal muscles and bones but requires daily injections or surgical implantation. Current clinical IGF-1 lacks e-peptide and is glycosylated, reducing functional efficacy. In this study, codon-optimized Pro-IGF-1 with e-peptide (fused to GM1 receptor binding protein CTB or cell penetrating peptide PTD) was expressed in lettuce chloroplasts to facilitate oral delivery. Pro-IGF-1 was expressed at high levels in the absence of the antibiotic resistance gene in lettuce chloroplasts and was maintained in subsequent generations. In lyophilized plant cells, Pro-IGF-1 maintained folding, assembly, stability and functionality up to 31 months, when stored at ambient temperature. CTB-Pro-IGF-1 stimulated proliferation of human oral keratinocytes, gingiva-derived mesenchymal stromal cells and mouse osteoblasts in a dose-dependent manner and promoted osteoblast differentiation through upregulation of ALP, OSX and RUNX2 genes. Mice orally gavaged with the lyophilized plant cells significantly increased IGF-1 levels in sera, skeletal muscles and was stable for several hours. When bioencapsulated CTB-Pro-IGF-1 was gavaged to femoral fractured diabetic mice, bone regeneration was significantly promoted with increase in bone volume, density and area. This novel delivery system should increase affordability and patient compliance, especially for treatment of musculoskeletal diseases.
Databáze: OpenAIRE
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