Evidence map›Paper›PMID 31870566›Full record

ArticleBiomaterials2020

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

J Park, G Yan, K-C Kwon, M Liu, P A Gonnella, S Yang, H Daniell

Open access · hybridAbstract read
In one paragraph

Article in Biomaterials, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
6.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

53 citing papers in PubMed, 75 citations in OpenAlex.

  1. Trial
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  3. Glucose metabolism in osteoporosis: A potential therapeutic target (Review).International journal of molecular medicine · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

J ParkDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
G YanDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
K-C KwonDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
M LiuDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
P A GonnellaDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
S YangDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; The Penn Center for Musculoskeletal Disorders, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: shuyingy@upenn.edu.
H DaniellDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: hdaniell@upenn.edu.
University of Pennsylvania · US

Funding

Oral immune modulatory therapy using antigens bioencapsulated in plant cellsR01HL107904 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DANIELL, HENRY · 2011 to 2023
$7.5M
Oral Therapy for Hemophilia AR01HL109442 · NHLBI · UNIVERSITY OF FLORIDA · PI DANIELL, HENRY, HERZOG, ROLAND W. · 2011 to 2015
$3.5M
Oral Tolerance for HemophiliaR01HL133191 · NHLBI · UNIVERSITY OF FLORIDA · PI DANIELL, HENRY, HERZOG, ROLAND W. · 2017 to 2020
$2.8M
Expression of Human Therapeutic Proteins in Transgenic Tobacco ChloroplastsR01GM063879 · NIGMS · UNIVERSITY OF CENTRAL FLORIDA · PI DANIELL, HENRY · 2002 to 2010
$2.0M
Regulation of skeletal development and homeostasis by IFT proteinR01DE023105 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI YANG, SHUYING · 2014 to 2018
$2.0M
Role of RGS12, a Regulator of G protein Signaling, in Bone RemodelingR01AR066101 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI YANG, SHUYING · 2014 to 2018
$1.8M
NHLBI NIH HHS R01 HL107904NHLBI NIH HHS R01 HL109442NHLBI NIH HHS R01 HL133191NIAMS NIH HHS R01 AR066101NIDCR NIH HHS R01 DE023105NIGMS NIH HHS R01 GM063879
6 · The paper itself

Abstract

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.

Indexed as

Diabetes Mellitus, ExperimentalFracture HealingLactucaAdministration, OralAnimalsCell DifferentiationCell ProliferationCells, CulturedFractures, BoneHumansInsulin-Like Growth Factor IMiceOsteoblastsInsulin-Like Growth Factor IBioencapsulation in plant cellsChloroplastHuman growth hormonesMusculoskeletal diseasesOral biopharmaceutical delivery

Identifiers

PMID31870566
PMCPMC6990632
OpenAlexW2984473197

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.