Artificial pancreas ... an option

Coming Soon: 'Artificial Pancreas' Options for Diabetes

Miriam E Tucker

June 20, 2016

 

NEW ORLEANS — Nearly closed-loop systems (also referred to as an "artificial pancreas") for improving glycemic control and minimizing hypoglycemia in type 1 diabetes are advancing rapidly, including iterations that deliver insulin alone, insulin with glucagon, or glucagon alone.

Findings for several of the products in development demonstrating improvements in glycemic control and reductions in hypoglycemia were presented here at the American Diabetes Association (ADA) 2016 Scientific Sessions.

"Some people may do well on insulin only, while others may need glucagon," Vincent Crabtree, PhD, director of the artificial pancreas program at JDRF, in New York, told Medscape Medical News, adding, "JDRF would like people to have choice, and we'd like all to be covered [by payers]."

The insulin-only hybrid closed-loop 670G system (Medtronic MiniMed) is the furthest along in development, and pivotal trial results were presented during a late-breaking poster session. Premarket approval submission with the US Food and Drug Administration is anticipated this summer.

Not far behind is the "bionic pancreas," a term originally coined by Boston University biomedical engineering professor Edward R Damiano, PhD, and colleagues for their system that dispenses both insulin and glucagon. Now a fully integrated dual-chamber device called the iLet, it is being further developed by Beta Bionics, a public-benefit corporation that Dr Damiano recently cofounded.

Dr Vincent Crabtree

Data presented at the meeting for the iLet included its use as a single-hormone device, with insulin only and glucagon only, as well as its dual-chamber use.

Beta Bionics is working with Denmark-based Zealand Pharma to develop a more stable glucagon analog for use with the iLet, as the current formulation requires daily reconstitution. Because the regulatory pathway for that product is expected to take some time, the iLet device is likely to reach the market sooner with single-chamber indications, Laya Ekhlaspour, MD, a pediatric endocrinology fellow at Massachusetts General Hospital in Boston, explained.

"Waiting for approval of a more stable glucagon could delay this coming to market....We plan to start our pivotal study with an insulin-only version to get approval faster," Dr Ekhlaspour, who presented the iLet insulin-alone data at the meeting, told Medscape Medical News.

Courtney Balliro, RN, CDE, also at Massachusetts General Hospital, who presented the glucagon-only data, noted, "Creating a new drug takes a lot longer. We believe glucagon is necessary [in a closed-loop system], but we can help people in the meantime."

Indeed, Dr Crabtree said, "We don't know what's going to happen. We don't know if there will be a stable glucagon or if insurers will pay for it. So at the very minimum we need an insulin-only system."

He added that several other companies are also moving toward closed-loop systems, many with JDRF funding.

Hybrid Closed-Loop System ― First on Market by Year End?

The Medtronic 670G is a hybrid closed-loop system, meaning that the user must periodically calibrate it and give mealtime and correction insulin boluses as needed, while it takes care of background insulin delivery. The system consists of Medtronic's insulin pump, a fourth-generation continuous-glucose sensor, and a control algorithm.

In the pivotal study, reported as a late-breaking poster by Richard Bergenstal, MD, of Park Nicollet Methodist Hospital, in St Louis Park, Minnesota, 124 adolescent and adult patients with type 1 diabetes wore the hybrid closed-loop system, first for 6 days in a supervised hotel setting followed by 3 months at home.

While using the 670G, patients spent 24.5% of the time with sensor glucose values above 180 mg/dL compared with 27.4% of the time at baseline (P < .001); equivalent figures were 3.3% vs 5.9% for glucose below 70 mg/dL (P < .001) and 0.6% vs 1.0% for glucose at or below 50 mg/dL (P < .001).

Very similar results were seen for sensor values between 10:00 pm and 7:00 am (all P < .001).

None of the patients developed diabetic ketoacidosis, severe hypoglycemia, or serious device-related adverse events during 12,389 patient-days. After the study ended, 99 patients entered a program that allowed them to continue using the system.

"Our hybrid closed-loop system is designed to automate the delivery of insulin and has undergone rigorous evaluation in the largest and longest at-home closed-loop study....We are the first company to complete a pivotal trial on artificial-pancreas technology and will be filing a premarket approval submission to the FDA in the coming weeks," study coauthor Francine R Kaufman, MD, vice president of Global Medical Affairs for Medtronic Diabetes, Los Angeles, California, said in a statement to Medscape Medical News.

Glucagon-Only Delivery

Dr Courtney Balliro

Meanwhile, Ms Balliro presented her data on the closed-loop glucagon-only system during the ADA president's oral abstract session. Here, with only the glucagon chamber filled, the iLet delivers very small doses of glucagon in response to sensor-detected hypoglycemia.

In the double-blind, placebo-controlled, crossover study, 22 adults with type 1 diabetes with reduced hypoglycemia awareness were randomized to glucagon (mean dose 0.5 mg/day, about half the usual rescue dose) or placebo, along with using their own insulin pumps or multiple daily insulin injections, for 7 days.

Overall, there was a 75% reduction in time spent in hypoglycemia (< 60 mg/dL), 1.2% with the glucagon system vs 4.7% with placebo (P < .0001). Nocturnal hypoglycemia was reduced by 91% to just 0.5% from 5.4% with placebo (P < .0001).

At the same time, there was no increase in mean glucose levels recorded by the continuous-glucose monitor (153 vs 152 mg/dL, P = .60), nor did patients report excess nausea, vomiting, headache, or skin infections on glucagon days.

"The glucagon was tolerated very well," Ms Balliro noted.

In addition to pursuing the glucagon-delivery system as a stand-alone and ― as part of the dual-hormone device for people with diabetes ― the group also plans to study the glucagon-alone system in people with conditions for which they would not require insulin delivery, including postbariatric surgery hypoglycemia or congenital hyperinsulinism.

"We're looking to expand our research to include those folks, too," she concluded.

Insulin-Only System, With Slightly Higher Glucose Targets

Dr Laya Ekhlaspour

Dr Ekhlaspour presented findings from a random-order crossover iLet study in 20 adults with type 1 diabetes. The study compared six 3-day arms: two insulin-only configurations of the device (glucose targets of 130 and 145 mg/dL) with a bihormonal configuration (glucose targets of 100, 115, or 130 mg/dL) and usual care (patient-managed insulin-pump therapy). Glucose targets were set higher for the insulin-only configuration, to minimize the risk of hypoglycemia when glucagon was not present.

Study patients carried out their usual daily routines with no restrictions on food or exercise during each test period.

Mean glucose was higher for the insulin-only pump group for the 145 mg/dL vs the 130 mg/dL target with configuration, or for usual care (P < .0001 to .034), but there were no significant differences among groups in time spent with blood glucose below 60 mg/dL (all P > .28).

The Boston team is currently comparing the insulin-only and bihormonal configurations with a target glucose of 110 mg/dL, Dr Ekhlaspour said.

Bionic Pancreas: As Little Patient Involvement As Possible

Dr Damiano presented data from a multicenter study in 39 patients who wore the dual-hormone 'bionic pancreas' system for 11 days at home with no restrictions on food or activity.

As he reported last year at the American Association of Clinical Endocrinologists' 2015 Annual Scientific and Clinical Congress, mean glucose levels were lower with the dual-hormone iLet compared with standard pump therapy (141 vs 162 mg/dL; P < .0001), and time spent in hypoglycemia (< 60 mg/dL) was reduced with the dual-hormone iLet (0.6% vs 1.9%; P < .0001).

Over the study period, the iLet was associated with a reduction in mean number of symptomatic hypoglycemia events per day (0.59 vs 0.90; P = 0.023).

Dr Damiano explained that the dual-hormone iLet differs from the Medtronic system in the degree of patient input required. For the iLet, the person simply inputs their body weight and the device essentially takes over, whereas the Medtronic 670G still requires the user to count carbs, take an insulin bolus before meals, and program their insulin doses.

The "bionic pancreas" also has an optional meal announcement, whereby the person simply inputs whether an upcoming meal is bigger, smaller, or about the same size as usual. But the system will compensate even if the person forgets to do that, he said during a press briefing.

"The device is designed to involve as little involvement from the patient as possible....It doesn't care about your skill set," he commented.

Coming Soon

Dr Edward Damiano

At least two other companies, Tandem and Bigfoot Biomedical, have also announced late-stage testing of partially closed-loop systems.

"Remember what the first cellphones were like. Things get better over time, and this is part of the natural technology evolution....So in a few years there will be several to choose from. You'll be able to choose based on the pros and cons of each," Dr Crabtree said.

He cautioned, though, that the cost of glucagon for the iLet could present an obstacle.

"We don't know what's going to happen to the healthcare system in the future. It may be that you can get an insulin-only system with your insurance and if you want glucagon you have to pay out of pocket. Or maybe [the healthcare system] will pay for glucagon but only if the physician says you need a glucagon system," such as for people with hypoglycemic unawareness or who exercise frequently.

In all, he said, "Each person's diabetes is unique....Just one type of system won't work for everybody. It's better to have the choice."

Dr Crabtree is an employee of the JDRF, which funds several companies involved in closed-loop system development. Dr Damiano is cofounder and shareholder of Beta Bionics. Ms Balliro and Dr Ekhlaspour have reported no relevant financial relationships. Dr Bergenstal receives research support from Medtronic. Dr Kaufman is an employee of Medtronic. Disclosures for the coauthors are listed in the abstracts.

American Diabetes Association (ADA) 2016 Scientific Sessions; June 14, 2016; New Orleans, Louisiana. Abstracts 77-OR, 79-OR, 99-LB, 378-

www.medscape.com

Erythropoietin as a Retinal Angiogenic Factor in Proliferative Diabetic Retinopathy

Although vascular endothelial growth factor (VEGF) is a primary mediator of retinal angiogenesis, VEGF inhibition alone is insufficient to prevent retinal neovascularization. Hence, it is postulated that there are other potent ischemia-induced angiogenic factors. Erythropoietin possesses angiogenic activity, but its potential role in ocular angiogenesis is not established.

METHODS

We measured both erythropoietin and VEGF levels in the vitreous fluid of 144 patients with the use of radioimmunoassay and enzyme-linked immunosorbent assay. Vitreous proliferative potential was measured according to the growth of retinal endothelial cells in vitro and with soluble erythropoietin receptor. In addition, a murine model of ischemia-induced retinal neovascularization was used to evaluate erythropoietin expression and regulation in vivo.

RESULTS

The median vitreous erythropoietin level in 73 patients with proliferative diabetic retinopathy was significantly higher than that in 71 patients without diabetes (464.0 vs. 36.5 mIU per milliliter, P<0.001). The median VEGF level in patients with retinopathy was also significantly higher than that in patients without diabetes (345.0 vs. 3.9 pg per milliliter, P<0.001). Multivariate logistic-regression analyses indicated that erythropoietin and VEGF were independently associated with proliferative diabetic retinopathy and that erythropoietin was more strongly associated with the presence of proliferative diabetic retinopathy than was VEGF. Erythropoietin and VEGF gene-expression levels are up-regulated in the murine ischemic retina, and the blockade of erythropoietin inhibits retinal neovascularization in vivo and endothelial-cell proliferation in the vitreous of patients with diabetic retinopathy in vitro.

CONCLUSIONS

Our data suggest that erythropoietin is a potent ischemia-induced angiogenic factor that acts independently of VEGF during retinal angiogenesis in proliferative diabetic retinopathy.

Article:-

Pathologic growth of new blood vessels is a common final pathway in ocular neovascular diseases, such as proliferative diabetic retinopathy, that often result in catastrophic loss of vision. Vascular endothelial growth factor (VEGF) is a primary angiogenic factor that mediates such ischemia-induced retinal neovascularization. VEGF levels are elevated in the vitreous fluid of patients with proliferative diabetic retinopathy, and VEGF induces proliferation in vascular endothelial cells in vitro.¹ Although inhibition of VEGF reduces retinal neovascularization,^2,3 it does not completely inhibit ischemia-driven retinal neovascularization. Thus, the involvement of other angiogenic factors in this process seems likely.

The glycoprotein erythropoietin stimulates the formation of red cells by enhancing both their proliferation and their differentiation and by preventing apoptotic death of erythropoietin-responsive erythroid precursor cells.^4-6 A major signal that regulates the production of erythropoietin in these tissues is hypoxia, and the brain has a paracrine system involving erythropoietin and erythropoietin receptors, suggesting that erythropoietin contributes to the survival of neurons by protecting them from ischemic damage.^7-9 Furthermore, erythropoietin shows angiogenic activity in vascular endothelial cells, stimulating proliferation, migration, and angiogenesis in vitro, probably by means of the erythropoietin receptor expressed in those cells.^10,11 Such angiogenic activity involves several signal-transduction cascades such as extracellular signal-regulated kinase, Janus kinase 2 (known as JAK2), and signal transducer and activator of transcription 5 (STAT5).^12-15 Moreover, the inhibition of erythropoietin by soluble erythropoietin receptor abrogates angiogenesis in vivo.^16,17

Since erythropoietin is an ischemia-induced paracrine factor that promotes angiogenesis, we wished to identify its potential role during retinal angiogenesis in proliferative diabetic retinopathy. Therefore, we examined in vitro the expression and function of erythropoietin in the vitreous fluid of patients with proliferative diabetic retinopathy and evaluated the role of erythropoietin in an in vivo experimental model of retinal angiogenesis. Our data provide strong evidence that erythropoietin is a potent retinal angiogenic factor independent of VEGF and is capable of stimulating ischemia-induced retinal angiogenesis in proliferative diabetic retinopathy.

Daisuke Watanabe, M.D., Ph.D., Kiyoshi Suzuma, M.D., Ph.D., Shigeyuki Matsui, Ph.D., Masafumi Kurimoto, M.D., Junichi Kiryu, M.D., Ph.D., Mihori Kita, M.D., Ph.D., Izumi Suzuma, M.D., Ph.D., Hirokazu Ohashi, M.D., Ph.D., Tomonari Ojima, M.D., Tomoaki Murakami, M.D., Toshihiro Kobayashi, Ph.D., Seiji Masuda, Ph.D., Masaya Nagao, Ph.D., Nagahisa Yoshimura, M.D., Ph.D., and Hitoshi Takagi, M.D., Ph.D.

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August 25, 2005

N Engl J Med 2005; 353:782-792

www.nejm.com

New Aspirin Guide Mobile app helping clinicians and patients... both

New Aspirin-Guide mobile app helps clinicians and patients make informed decisions about aspirin use

Posted in: Device / Technology News | Medical Research News | Medical Condition News | Pharmaceutical News

Published on June 21, 2016 at 12:15 PM

Low dose aspirin is recommended by clinicians as a preventive measure for patients who have already had a heart attack or stroke, but the risk of taking low-dose aspirin to prevent or delay a first heart attack or stroke is less clear, as the benefit for reducing the risk of cardiovascular disease (CVD) must be balanced with the increased risk of gastrointestinal or other bleeding. To help clinicians and patients make informed decisions about aspirin use, researchers at Brigham and Women's Hospital have developed a new, free, mobile app, "Aspirin-Guide" that calculates both the CVD risk score and the bleeding risk score for the individual patient, and helps clinicians decide which patients are appropriate candidates for the use of low-dose aspirin (75 to 81 mg daily).

"We developed the Aspirin-Guide app because we realized that weighing the risks and benefits of aspirin for individuals who have not had a heart attack or stroke is a complex process. The new mobile app enables individualized benefit to risk assessment in a matter of seconds while the patient is with the physician," said Samia Mora, MD, cardiologist at BWH.

In a commentary published in JAMA in the June 20 issue, and a review in JAMA Internal Medicine published on the same day, co-authors Mora, and JoAnn Manson, MD, cardiovascular epidemiologist and Chief of Preventive Medicine at BWH, review the evidence behind the use of aspirin to delay or prevent a first heart attack of stroke, and give examples of how the mobile app can help patients and clinicians including:

•calculates a 10-year cardiovascular disease risk score (heart disease and stroke) for the patient
•calculates a bleeding risk score based on the patient's individual risk factors
•uses evidence from the literature, together with the above scores, to compare the number needed to treat vs. the number needed to harm
•helps clinicians to implement current clinical guidelines for low-dose aspirin in primary prevention
•provides the ability to email a summary of the decision-making process to the patient and/or to the clinician for the patient's record.

"Aspirin-Guide is a user-friendly clinical decision support tool, that will facilitate informed and personalized decision-making about the use of aspirin in primary prevention of CVD. Patients should discuss the pros and cons of aspirin treatment with their healthcare provider," Manson said.

Source: Brigham and Women’s Hospital

Penicillin redux: Rearming proven warriors for the 21st century

Penicillin, one of the scientific marvels of the 20^th century, is currently losing a lot of battles it once won against bacterial infections. But scientists at the University of South Carolina have just reported a new approach to restoring its combat effectiveness, even against so-called "superbugs."

Bacteria have been chipping away at the power of the penicillin family of drugs since their first wide-scale use as antibiotics in the 1940s. For example, the staph infection, brought about by the bacterium Staphylococcus aureus, was once readily treated with penicillin and its molecular cousins.
But that bug has changed. In the 1960s, a new strain arrived, termed MRSA for methicillin- (or sometimes multidrug-) resistant S. aureus. It has become a serious public health problem because the earliest deployed antibiotics are often useless against the new strain, and its prevalence has only increased since it was first observed. MRSA (pronounced mer-suh) is sometimes called a superbug because of the difficulty physicians have in treating infected patients.
The S. aureus microbe has evolved the MRSA strain by developing a variety of defenses against antibiotics to which they've been exposed. One of those defenses effectively neutralizes penicillin's greatest strength.
That strength is its molecular core, a cyclic four-membered amide ring termed a beta-lactam. It is a common structural element of the penicillins, their synthetic and semi-synthetic derivatives, and other related molecules that constitute the broad family of drugs called the beta-lactam antibiotics. Just a few examples (of dozens) include amoxicillin, ampicillin and cefazolin.
The beta-lactam structure in a molecule is something that many bacteria don't like at all. It greatly hinders their ability to reproduce by cell division, and so chemists have for years spent time making molecules that all contain the beta-lactam structural motif, but differ in the surrounding molecular "shrubbery." Physicians heavily use the many versions of beta-lactam antibiotics to fight bacterial infections, and many have been retired because they're no longer effective against the defenses bacteria have evolved in response.
One of the most effective bacterial defenses is an enzyme called beta-lactamase, which chews up the beta-lactam structure. Some bacteria, such as MRSA, have developed the ability to biosynthesize and release beta-lactamase when needed. It's a devastating defense because it's so general, targeting the common structural motif in all of the many beta-lactam antibiotics.
But that also creates the opportunity for a general approach to solving the problem, which is what Carolina's Chuanbing Tang and colleagues just reported in the Journal of the American Chemical Society.
"Instead of developing new antibiotics, here we ask the question, 'can we recycle the old antibiotics?' " he said. "With traditional antibiotics like penicillin G, amoxicillin, ampicillin and so on, can we give them new life?"
The approach pairs the drug with a protective polymer developed in Tang's chemistry laboratory. In lab tests, graduate student Jiuyang Zhang prepared a cobaltocenium metallopolymer that greatly slowed the destructiveness of beta-lactamase on a model beta-lactam molecule (nitrocefin).
The interdisciplinary team, which included Mitzi Nagarkatti and Alan Decho, from the university's School of Medicine and Arnold School of Public Health, respectively, also showed that the antimicrobial effectiveness of the four beta-lactams studied in detail was enhanced by the polymer. The enhancement was modest against two strains, but very pronounced with the hospital-associated strain of MRSA (HA-MRSA).
The metallopolymer by itself even demonstrated antimicrobial properties, lysing bacterial cells while leaving human red blood cells unaffected. By a variety of measures, the polymer was found to be nontoxic to human cells in laboratory tests.
The project is still far from clinical use, but Tang knows moving forward is imperative.
"In the United States every year, around 100,000 patients die of bacteria-induced infections," Tang said. "And the problem is increasing because bacteria are building resistance. It's a really, really big problem, not only for individual patients, but also for society."

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Story Source:
The above story is based on materials provided by University of South Carolina. The original article was written by Steven Powell. Note: Materials may be edited for content and length.

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Journal Reference:

1. Jiuyang Zhang, Yung Pin Chen, Kristen P. Miller, Mitra S. Ganewatta, Marpe Bam, Yi Yan, Mitzi Nagarkatti, Alan W. Decho, Chuanbing Tang. Antimicrobial Metallopolymers and Their Bioconjugates with Conventional Antibiotics against Multidrug-Resistant Bacteria. Journal of the American Chemical Society, 2014; 136 (13): 4873 DOI: 10.1021/ja5011338

Monoclonal Antibody Targets, Kills Leukemia Cells

Monoclonal Antibody Targets, Kills Leukemia Cells

 Researchers at the University of California, San Diego Moores Cancer Center have identified a humanized monoclonal antibody that targets and directly kills chronic lymphocytic leukemia (CLL) cells
The findings, published in the online Early Edition of the Proceedings of the National Academy of Sciences on March 25, 2013 represent a potential new therapy for treating at least some patients with CLL, the most common type of blood cancer in the United States.
CLL cells express high levels of a cell-surface glycoprotein receptor called CD44. Principal investigator Thomas Kipps, MD, PhD, Evelyn and Edwin Tasch Chair in Cancer Research, and colleagues identified a monoclonal antibody called RG7356 that specifically targeted CD44 and was directly toxic to cancer cells, but had little effect on normal B cells.
Moreover, they found RG7356 induced CLL cells that expressed the protein ZAP-70 to undergo apoptosis or programmed cell death. Roughly half of CLL patients have leukemia cells that express ZAP-70. Such patients typically have a more aggressive form of the disease than patients with CLL cells that do not express that specific protein.

Previous research by Kipps and others has shown that CLL cells routinely undergo spontaneous or drug-induced cell death when removed from the body and cultured in the laboratory. They found that CLL cells receive survival signals from surrounding non-tumor cells that are present in the lymph nodes and bone marrow of patients with CLL. One of these survival signals appears to be transmitted through CD44. However, when CD44 is bound by the RG7356 monoclonal antibody, it seems to instead convey a death signal to the leukemia cell.
"By targeting CD44, it may be possible to kill CLL cells regardless of whether there are sufficient numbers of so-called 'effector cells,' which ordinarily are required by other monoclonal antibodies to kill tumor cells," said Kipps. "We plan to initiate clinical trials using this humanized anti-CD44 monoclonal antibody in the not-too-distant future."
Co-authors were Suping Zhang, Christina C.N. Wu, Jessie-Farah Fecteau, Bing Cui, Liguang Chen, Ling Zhang, Rongrong Wu, Laura Rassenti, and Fitzgerald S. Lao, Department of Medicine, UCSD Moores Cancer Center; and Stefan Weigand, Roche Diagnostics GmbH, Germany.
Funding for this study came, in part, from the National Institutes of Health (grant PO1-CA081534) and the UC San Diego Moores Cancer Blood Center Research Fund.

Story Source:

The above story is reprinted from materials provided by University of California, San Diego Health Sciences.

Journal Reference:

1. Suping Zhang, Christina C. N. Wu, Jessie-F. Fecteau, Bing Cui, Liguang Chen, Ling Zhang, Rongrong Wu, Laura Rassenti, Fitzgerald Lao, Stefan Weigand, and Thomas J. Kipps. Targeting chronic lymphocytic leukemia cells with a humanized monoclonal antibody specific for CD44. PNAS, March 25, 2013 DOI: 10.1073/pnas.1221841110

Stem Cell Treatment May Become Option to Treat Nonhealing Bone Fractures

Stem Cell Treatment May Become Option to Treat Non healing Bone Fractures

Stem cell therapy enriched with a bone-regenerating hormone, insulin-like growth factor-I (IGF-I), can help mend broken bones in fractures that are not healing normally, a new animal study finds.
The results are being presented at The Endocrine Society's 93rd Annual Meeting in Boston.
A deficiency of fracture healing is a common problem affecting an estimated 600,000 people annually in North America, according to the principal investigator, Anna Spagnoli, MD, associate professor of pediatrics and biomedical engineering at the University of North Carolina at Chapel Hill.
"This problem is even more serious," Spagnoli said, "in children with osteogenesis imperfecta, or brittle bone disease, and in elderly adults with osteoporosis, because their fragile bones can easily and repeatedly break, and bone graft surgical treatment is often not successful or feasible"
Fractures that do not heal within the normal timeframe are called non-union fractures. Using an animal model of a non-union fracture, a "knockout" mouse that lacks the ability to heal broken bones, Spagnoli and her colleagues studied the effects of transplanting adult stem cells enriched with IGF-I. They took mesenchymal stem cells (adult stem cells from the bone marrow) of mice and engineered the cells to express IGF-1. Then they transplanted the treated cells into knockout mice with a fracture of the tibia, the long bone of the leg.
Using computed tomography (CT) scanning, the researchers showed that the treated mice had better fracture healing than did control mice either left untreated or treated only with stem cells. They found that the stem cells enriched with IGF-I became bone cells and helped the cells in the broken bones to repair the fracture, speeding the healing. Compared with controls left to heal on their own, treated mice had more bone bridging the fracture gap, and that new bone was three to four times stronger, according to Spagnoli.
"More excitingly, we found that stem cells empowered with IGF-I restored the formation of new bone in a mouse lacking the ability to repair broken bones. This is the first evidence that stem cell therapy can address a deficiency of fracture repair," she said.
This success in an animal model of fracture non-union, Spagnoli said, "is a crucial step toward developing a stem cell-based treatment for patients with fracture non-unions."
"We envision a clinical use of combined mesenchymal stem cells and IGF-1 similar to the approach employed in bone marrow transplant, in which stem cell therapy is combined with growth factors to restore blood cells," she said. "I think this treatment will be feasible to start testing in patients in a few years."
IGF-I is approved for treatment of children with a deficiency of this hormone, causing growth failure.
The National Institutes of Health supported this study through a NIDDK-NIH R01 grant.