Bioengineered Trachea Implanted into a Child


Hannah Genevieve Warren was born in 2010 in Seoul, South Korea with tracheal agenesis, which is to say that she was born without a trachea. Hannah had a tube inserted through her esophagus to her lungs that allowed her to breathe. Children with tracheal agenesis usually die in early childhood, 100% of the time. No child with this condition has ever lived past six years of life. Hannah spent the first two years of her life at the Seoul National Hospital before she was transported to Illinois for an unusual surgery.

While at the Children’s Hospital of Illinois, on April 9, 2013, Hannah had a bioengineered trachea transplanted into her body. This trachea was the result of a remarkable feat of technology called the InBreath tracheal scaffold and bioreactor system that was designed and manufactured by Harvard Bioscience, Inc. Harvard Bioscience, or HBIO, is a global developer, manufacturer and marketer of a broad range of specialized products, primarily apparatus and scientific instruments, used to advance life science research and regenerative medicine.

InBreath tracheal scaffold
InBreath tracheal scaffold

Hannah’s tracheal transplant was the first regenerated trachea transplant surgery that used a biomaterial scaffold that manufactured by the Harvard Apparatus Regenerative Technology (HART) Inc., a wholly owned subsidiary of Harvard Bioscience. HART ensured that the scaffold and bioreactor were custom-made to Hannah’s dimensions. Then the scaffold was seeded with bone marrow cells taken from Hannah’s bone marrow, and the cells were incubated in the bioreactor for two days prior to implantation. Because Hannah’s own cells were used, her body accepted the transplant without the need for immunosuppressive (anti-rejection) drugs.

InBreath Bioreactor
InBreath Bioreactor

The surgeons who participated in this landmark transplant were led by Dr. Paolo Macchiarini of Karolinska University Hospital and Karolinska Institutet in Huddinge, Stockholm and Drs. Mark J. Holterman and Richard Pearl both of Children’s Hospital of Illinois. This surgery was approved by the FDA under an Investigational New Drug (IND) application submitted by Dr. Holterman.

Dr. Mark Holterman, Professor of Surgery and Pediatrics at University of Illinois College of Medicine at Peoria, commented: “The success of this pediatric tracheal implantation would have been impossible without the Harvard Bioscience contribution. Their team of engineers applied their talent and experience to solve the difficult technical challenge of applying regenerative medicine principles in a small child.”

David Green, President of Harvard Bioscience, said: “We would like to congratulate Dr. Macchiarini, Dr. Holterman, Dr. Pearl and their colleagues for accomplishing the world’s first transplant of a regenerated trachea in a child using a synthetic scaffold and giving Hannah a chance at a normal life. We also wish Hannah a full recovery and extend our best wishes to her family.”

Hannah’s surgery is the seventh successful implant of a regenerated trachea in a human using HART technology. Prior successes included the first ever successful regenerated trachea transplant in 2008, the first successful regenerated trachea transplant using a synthetic scaffold in 2011, and the commencement of the first clinical trial of regenerated tracheas in 2012. HART has plans to commence discussions with the FDA and EU regulatory authorities in the near future regarding the clinical pathway necessary to bring this new therapeutic approach to a wider range of patients who are in need of a trachea transplant.

Stem Cell Treatments for Large Ankle Cartilage Lesions


The Regenexx blog has called attention to to a study that shows that older patients with ankle problems can benefit from mesenchymal stem cell treatments of the ankle.

The paper referenced by Centeno on his blog was published in the American Journal of Sports Medicine 2013 May;41(5):1090-9, and is entitled, “Clinical outcomes of mesenchymal stem cell injection with arthroscopic treatment in older patients with osteochondral lesions of the talus.” The authors of this paper are Kim YS, Park EH, Kim YC, Koh YG. who all hale from the Department of Orthopedic Surgery, Yonsei Sarang Hospital, Seoul, South Korea.

The paper notes that there are no generally accepted, ideal treatments for “osteochondral lesions of the talus”, which is in plain English means cartilage erosions of the large bone in the foot that articulates with the base of the lower leg bones. That bone, the talus, sits above the heel bone (calcaneus) and is covered with articular cartilage to absorb shocks that occur between blows from the fibula and tibia and the talus. Over time, wear and tear can erode this cartilage and the best way to go about fixing these osteochondral lesions of the talus or OLTs as they are called, is not at all clear. Centeno mentions in his blog that he and his colleagues have been treating OLTs with mesenchymal stem cells for some time (since 2006). In this paper, Kim and others tested the ability of bone marrow mesenchymal stem cells (MSCs) to provide relief from OLT.

ankle_anatomy_bones01

Kim and colleagues compared the outcomes of patients who had received MSC injections and arthroscopic marrow stimulation treatments against the outcomes of those patients who had received only arthroscopic marrow stimulation treatment alone.

In this study, from a starting group of 107 patients with OLTs that were treated arthroscopically, only those patients older than 50 years (65 patients) were included in this study. Kim and others divided the patients into 2 groups: 35 patients (37 ankles) were treated with arthroscopic marrow stimulation treatment alone (group A) and 30 patients (31 ankles) who underwent MSC injection along with arthroscopic marrow stimulation treatment (group B).

The clinical outcomes for these patients were assessed according to the visual analog scale (VAS) for pain, but there were other measurements as well. For example, how active were the patients? A Tegner score determined how active patients were, which is important because the more active a patient is, the less likely they are to be in pain. Other assessments included the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale, which measures how well you walk and how much pain you experience when you do it, and other scores for the foot and how well it works

The outcomes for the study were as follows. Both groups showed a decrease in pain. Group A had a VAS score that started at 7.2 ± 1.1 and fell to 4.0 ± 0.7, whereas group B started at 7.1 ± 1.0 and decreased to 3.2 ± 0.9. Therefore the patients in group B showed a slightly greater decrease in pain over the non-MSC group.

As for the AOFAS score in each group, which measures ankle function and pain while using the ankle, again, both groups showed improvement. Patients in group A went from 68.0 ± 5.5 to 77.2 ± 4.8, and patients in group B went from 68.1 ± 5.6 to 82.6 ± 6.4. Thus the patients who received the MSC treatments used their ankles better than those patient who did not receive MSC treatments, and they also used their ankles with less pain.

A different measure of ankle function, the Roles and Maudsley score, also increased significantly in group A patients as opposed to group A patients at postsurgical follow up (1-4 years after the surgery). However, the real “money” finding of this research was that the patients who had received the MSC injections were significantly more active after surgery than the non-MSC patients. The activity score in patients from group A. Group A patients had a Tegner activity score that went from 3.5 ± 0.8 to 3.6 ± 0.6. That is not a significant increase. However the patients in group B, who had received the injections of their own MSCs into the ankle, had Tegner activity scores that improved from 3.5 ± 0.7 to 3.8 ± 0.7 (P = .041). Thus the patients who had received the MSC injections had less pain, better ankle function with less pain, better ankle and foot function 1-4 years after surgery, and were significantly more active after surgery.

From these data, the authors concluded that injection of MSCs with marrow stimulation treatment was a treatment option in patients older than 50 years than marrow stimulation treatment alone. THis was especially the case if the OTL was larger than 109 square millimeters. Also, those patients in group A who had subchondral cysts did not fare well with their treatment, but there was no such correlation between a poor clinical outcome and the presence of a subchondral cyst in patients from group B.

subchondral cyst in the ankle
subchondral cyst in the ankle

Therefore, even though MSC treatments for OTLs is still in its early stages of development, they seem to have the potential to treat of OLTs in patients older than 50 years. However, this study, while not tiny, is still not all that large, and larger studies are warranted.