Author: Beverly Meyer

Clinical Experience

World’s First Human Transplant of a Regenerated Airway

In 2008, our InBreath airway bioreactor technology was used to perform the world’s first human transplant of a regenerated airway. The surgery was conducted by Dr. Macchiarini and his team of surgeons in Barcelona, Spain. The patient had suffered a collapse of her airway following a severe tuberculosis infection. To create the regenerated airway, a donor trachea was obtained and stripped of its cells, and then the patient’s own bone marrow cells were used to seed the donor trachea and prepare it for implantation. Following such regeneration, the regenerated airway was then implanted into the patient. This patient recently passed the five-year survival point. In addition to improving her breathing, because the cells used in the transplant were her own cells taken from her own bone marrow, she has not had to take anti-rejection drugs after the surgery. This surgery was published in The Lancet in November 2008.

World’s First Successful Transplantation of a Synthetic Tissue Engineered Trachea

In June 2011, our InBreath bioreactor was used for the world’s first successful transplantation of a synthetic tissue engineered trachea. For the first time in history, a patient was given a new trachea made from a synthetic scaffold seeded with his own cells and grown in our bioreactor. The operation was performed at the Karolinska University Hospital in Stockholm, Sweden by Dr. Paolo Macchiarini and his team of surgeons. The patient had been suffering from late-stage trachea cancer, which before the surgery would have been inoperable. He was given only a few weeks to live and as such the transplant surgery using our product was a last-resort measure to save the patient’s life. The patient required a tracheo-bronchial scaffold transplant, whereby the scaffold mimics the branched shape of the airway. To create the new synthetic trachea, Dr. Alex Seifalian and other scientists at University College London developed a plastic scaffold shaped like the patient’s natural airway and Dr. Macchiarini seeded it with the patient’s own bone marrow cells. This seeding process prepared the synthetic trachea for implantation and thereafter the regenerated synthetic trachea was implanted into the patient. Because the cells used to regenerate the trachea were the patient’s own, there has been no rejection of the transplant, and, like the first patient described above, this patient is not taking anti-rejection drugs. This patient recently passed the two-year survival point. This surgery was published in The Lancet on November 24, 2011.

World’s Second Successful Transplantation of a Synthetic Tissue Engineered Trachea

In November 2011, the InBreath bioreactor was again used by Dr. Macchiarini to seed the cells on a synthetic scaffold to treat a patient who was suffering from late-stage trachea cancer and required a tracheo-bronchial transplant. The operation was performed at the Karolinska University Hospital by Dr. Macchiarini and his team of surgeons. The procedure was similar to the world’s first successful transplantation of a synthetic tissue engineered trachea performed in June 2011, with the exception that the plastic scaffolding material was changed to a fiber construction rather than a porous solid construction. The fibrous scaffold seeded in the bioreactor for this November 2011 procedure was manufactured in a different laboratory than the one made for the June 2011 patient by another company. The patient recovered well from the transplant surgery and was discharged home from the hospital. Approximately four months after the surgery, the patient passed away from pneumonia secondary to a tracheal tumor. There is no indication that our bioreactor or the third-party scaffold played any role in his death. This patient, like the June 2011 patient, had undergone extensive radiation and chemotherapy treatment prior to the transplant, and his tumor was not responsive to these forms of treatment.

3rd Generation Synthetic Engineered Tracheas resulted in a number of Successful Transplantations

In November 2013, HART developed a third generation synthetic trachea. We believe that the new scaffolds are superior in quality compared to those used in surgeries prior to 2013. The scaffolds have several novel features including the sandwiching of stiff rings between layers of porous fabric to simulate the natural rigidity and flexibility of the natural trachea.

The Need for Synthetic Tracheas

HART is a clinical stage regenerative medicine company developing organs for transplant.

The first product, the InBreathTM Airway Transplant System, is intended to be used to restore the structure and/or function of a severely damaged airway. The InBreath System is comprised of a porous plastic scaffold made in the size and shape of the natural trachea, bronchus or tracheobronchial tree and a rotating bioreactor used to seed the patient’s own bone marrow cells onto the scaffold prior to implant.

We believe the InBreath System is the first to enable the application of regenerative medicine techniques to the production and transplant of complex, three-dimensional human organs like the trachea. The InBreath bioreactor technology has been used in excess of ten successful human airway transplant surgeries and the most recent of these surgeries also used our InBreath scaffold.

We believe that the first of the surgeries conducted in 2008, was the world’s first transplant of a regenerated airway. This surgery used a human donor trachea as the scaffold. In addition, we believe the second surgery, conducted in 2011, was the world’s first transplant of a regenerated airway using a synthetic scaffold.

The patients who received these two airway transplants are alive at more than five years and more than two years, respectively, following their surgeries, and each of these surgeries was published in The Lancet, one of the world’s most respected peer-reviewed medical journals. The third, fourth, fifth and sixth surgeries also used our bioreactors and used a second generation synthetic scaffold that was made of fabric rather than the solid/porous construction used in the second surgery. As of September 9, 2013 three of these four patients are alive. The one who did not survive died of underlying causes unrelated to the bioreactor or scaffold. The seventh, eighth, ninth and tenth surgeries used our bioreactors and third generation scaffolds, which were the first scaffolds manufactured by HART to be used in any human surgeries. Three of these four patients are alive. The one who did not survive died of underlying causes unrelated to the bioreactor or scaffold.

The first six surgeries took place in Europe and Russia. The seventh surgery was the first in the US and took place in April 2013 at Children’s Hospital of Illinois in Peoria with FDA approval under an investigator-led Investigational New Drug application, or IND. The three subsequent surgeries were performed in the third calendar quarter of 2013 in Europe and Russia. All surgeries to date using our technologies have been led by Professor Paolo Macchiarini, a world-renowned thoracic surgeon of the Karolinska Institutet, one of Europe’s leading research hospitals.

Our products are currently in development and have not yet received regulatory approval for sale anywhere in the world.

We believe our technology could enable surgeons to cure nearly all primary trachea cancers. Our products address the critical challenges to trachea transplant: the shortage of suitable donor tracheas and the risk and expense of lifelong anti-rejection drug therapy. Because the scaffolds are synthetic, our technology will eliminate the need to wait for suitable donor tracheas. Our technology also obviates the need for anti-rejection drug therapy because the surgeon uses the patient’s own bone marrow cells to seed the scaffold. In addition, patients with trachea cancer treated using our products have not required either chemotherapy or radiation therapy after the transplant, thus potentially eliminating the significant side effects and expense of such therapies.

Because these substantial costs and risks can be reduced or even eliminated with our technology, we believe our products can both help save lives and reduce overall healthcare costs. None of the surgeries using our products have involved human embryonic stem cells and we do not currently expect surgeons to use such cells with our products.

Trachea cancer is a devastating and almost always fatal disease. Current treatments such as radiation therapy, chemotherapy and surgery have poor outcomes, resulting in median survival of only 10 months and a five-year survival rate of only 15%. Trachea cancer is one of the most fatal of all cancers with 5-year survival rates far below those of breast cancer, prostate cancer or colon cancer. Surgically removing a tracheal tumor is often the best way to treat tracheal cancer. However, surgery generally cannot be performed if the tumor is more than 2cm (about ¾ of an inch) in diameter because the remaining tissue cannot be stretched enough to bridge the gap left by removing the tumor. Because it is hard to detect trachea cancer in its early stages, many patients are only diagnosed when the tumor is already too large to be surgically removed. In these cases the patients receive palliative treatment only and typically survive less than a year. These patients are the vast majority of trachea cancer patients and we believe that the InBreath Airway Transplant System could enable surgeons to cure nearly all primary trachea cancers.

According to an article published in The Annals of Surgical Oncology in 2009, the incidence of trachea cancer is approximately one per one million of population, reflecting an addressable market of approximately 900 trachea cancer patients per year in the developed world. In addition, the incidence of bronchial cancers is estimated in published articles to range from 0.1% to 2% of lung cancers. We believe we have been conservative in estimating the number of bronchial cancers at 0.2% of lung cancers reflecting an addressable market of approximately 1,500 bronchial cancer patients per year in the developed world. Therefore, we estimate the total addressable market for trachea and bronchus cancer combined is approximately 2,400 patients per year in the developed world. In addition to trachea cancer, certain types of trachea damage can be treated by transplanting a trachea. In particular, patients may receive a tracheotomy, or surgically created hole in their throat, to allow them to breathe. When the tracheotomies are in place for more than a few days, patients are at increased risk of dying from pneumonia caused by aspiration of foreign material into the lungs. We estimate that there are approximately 3,900 trachea damage patients per year worldwide. In addition, there are approximately 250 patients in the developed world who are born without a trachea, a condition called tracheal agenesis, who may be treatable with a trachea transplant.

Combining patients with trachea and bronchial cancer, trachea trauma and tracheal agenesis, we estimate the total addressable patient population for airway transplants using our products is approximately 6,500 per year. While we cannot predict what the total potential market will be when and if we obtain regulatory approval to market our trachea products, based solely on there being at least 6,500 patients per year at the time of such approval, we estimate the total potential market for airway transplants that use our products could exceed $600 million per year if we were able to charge at least $100,000 per procedure for the InBreath System. While these estimates capture the number of new patients annually that are candidates for transplants using our products, they exclude what we believe to be a much larger pool of existing potential patients.

Patients with trachea cancer typically are treated with radiation therapy, chemotherapy or a combination of both. There are a number of common significant side effects of radiation therapy and chemotherapy, including pain, fatigue, hair loss and kidney and bladder problems. Such therapies are also expensive, with chemotherapy alone typically costing $24,000 per patient annually. Even with these therapies median survival is only 10 months.

While surgery is a preferred treatment option for trachea cancer, it is rarely performed because most trachea cancers are not diagnosed until it is too late for surgery to be a viable option. A trachea or bronchus transplant has also not been a viable option to date due to the difficulties of finding an anatomical match between the donor and the patient. Even if a donor trachea were available, the patient would require anti-rejection drugs for the remainder of his or her life to prevent rejection of the donor trachea. This therapy is expensive, typically costing $20,000 to $30,000 per patient annually. There is also a risk to the patient as anti-rejection drugs suppress the immune system causing even a mild infection to become potentially life threatening.

Previous attempts to implant a tracheal prosthetic have been unsuccessful in improving long-term survival as they have been unable to allow the body to create a functional lining of the trachea which is essential to the clearance of mucus. Without the clearance of mucus, patients have poor prognosis and typically die from pneumonia or respiratory failure shortly after transplant.

Patients that contract aspiration pneumonia caused by tracheotomies are treated with antibiotics that often fail, leading to the death of the patient. Trachea transplant is almost never used to treat these patients today due to the lack of suitable donor tracheas.

Nearly all patients that are born without a trachea die within a few minutes of birth due to lack of oxygen. On rare occasions a hole forms between the patient’s esophagus and lungs that can allow a surgeon to insert a breathing tube to connect the lungs with the mouth. However, we know of no patient born with tracheal agenesis who has survived more than six years.

Our Solution

We believe the use of the medical device products we are currently developing, together with the patient’s own cells, will provide a system for surgeons that is a major advance over the current therapeutic options for treating trachea cancer and trachea trauma and may be applicable to other medical conditions requiring organ transplants. We believe our products are the first to enable the application of regenerative medicine techniques to the production and transplant of complex, three-dimensional organs like the trachea. With continued development, we believe that our technologies will be applicable to the repair or transplant of other important human organs such as the lungs, gastrointestinal tract, heart valves, and heart. Our bioreactor technology was used in both the world’s first transplant of a regenerated airway in 2008 and in the world’s first transplant of a synthetic regenerated airway in 2011. The complete InBreath System combining our scaffolds with our bioreactors was used for the first time in April 2013.

We believe our products will overcome the major challenges in trachea and other organ transplantation. Unlike traditional organ transplants, our products will eliminate the need for a donor because the scaffold will be manufactured in a factory. In addition, for hollow organs, such as the trachea, our technology enables the production of a transplant that precisely matches the patient’s anatomy. Because the surgeon uses the patient’s own bone marrow cells to seed the scaffold, our technology also eliminates the risk and expense of lifelong anti-rejection drug therapy. In addition, patients with trachea cancer treated using our products have not required either chemotherapy or radiation therapy after the transplant, thus eliminating the significant side effects and expense of such therapies. Because these substantial costs can be reduced or even eliminated with our technology, we believe our products can both help save lives and reduce overall healthcare costs.

Further, human embryonic stem cells have not been used in any of the procedures involving our trachea transplant products. This eliminates both the medical risks and ethical controversy associated with regenerative medicine approaches using human embryonic stem cells and other controversial sources of cells.

We believe the use of our products together with the patient’s own bone marrow cells solves both the major challenges facing organ transplant: a synthetic scaffold avoids the need to wait for a donor and the use of the patient’s own cells avoids the risk and costs of anti-rejection drug therapy. The first application of our products is in treating trachea cancer but we believe the technology can be developed to apply to other important human organ transplants as well.

Home / General Videos OnLine General Videos

Feb 12, 2011 Video National Geographic Explorer How to build a beating Heart
Feb 26, 2011 Video NOVA Science NOW Replacing Body Parts
Mar 10, 2012 The Lancet Paolo Macchiarini: Crossing Frontiers
Jan 20, 2012 Audio NPR – Science Friday Paolo Macchiarini M.D. Synthetic Windpipe Transplant Boost for Tissue Engineering

Home / Surgeries Surgeries & Related Media

2013-April Two year old Hannah Warren
July 8, 2013 HARVARD BIOSCIENCE Harvard Bioscience Comments on Regenerated Trachea Recipient Hannah Genevieve Warren’s Passing
July 8, 2013 HUFFPOST Toddler Who Received Windpipe Made From Stem Cells Dies
May 13, 2013 MP3 WCBS Newsradio 880 Interview
April 30, 2013 CBS News 2 year old gets windpipe made from her own stem cells
April 30, 2013 MSNBC 2 year old girl gets new life with windpipe from stem cells
April 30, 2013 Korean Herald Waiting on Life’s Breath
April 30, 2013 International Business Times Hannah Warren: 2 year old Toddler born without a windpipe
April 30, 2013 Today Show NBC Two Year Old Girl A Pioneer after Revolutionary Surgery
April 30, 2013 New York Times Ground Breaking Surgery for girl born without windpipe
2012-August Krasnodar Surgeries Julia Tulic & Aleksander Zozula
June 27, 2012 The New Scientist First Synthetic Larynx transplanted
June 26, 2012 Bloomberg Harvard Bioscience’s “InBreath” Bioreactors Used in World’s First Successful Regenerated Laryngotracheal
June 26, 2012 NASDAQ World’s First Artificial Windpipe May Open Door to more procedures
June 26, 2012 Boston Business Journal Harvard Bioscience’s stem cells in Russian Tracheal Transplants
June 22, 2012 Video Russian TV Channel 1 Unique operation on a Human – the patient started talking after a transplant of a trachea and part of the throat
Sept 17, 2012 Video EuroVision Supercells
2011-June Andemariam Tekesenbet Beyene
Jan 13, 2012 Medical News Today Artificial Trachea Patient doing well five months after procedure
Nov 25, 2011 Karolinska Univ Hospital First Successful Transplantation of a Synthetic Tissue Engineered Windpipe
July 8, 2011 CNN Health Lab-Made Organ implanted for the first time
July 8, 2011 Wired co UK News Second First Synthetic Trachea Transplant is a success in Sweden
July 8, 2011 Wall Street Journal Trachea Saves Man
July 8, 2011 New Scientist Health Man receives world’s first synthetic windpipe
July 7, 2011 Bloomberg World’s First Laboratory-Grown Windpipe Is Transplanted in Patient
Video Reuters World’s first synthetic trachea patient hails life-saving surgery
July 27, 2011 Video VOAvideo UTube Human Trachea from stem cells transplanted into cancer patient
Sept 15, 2012 New York Times A First: Organs Tailor-Made With Body’s Own Cells
2011-November Chris Lyles
Mar 6, 2012 Harvard Apparatus Harvard Bioscience Comments on the Passing of Christopher Lyles
July 7, 2011 BBC News Health First synthetic Organ Transplant
Jan 13, 2012 Baltimore Sun Abington Man first in the US to get synthetic trachea transplant
Jan 14, 2012 Mail OnLine “I’m going further everyday” Cancer patient’s joy after pioneering stem cell trachea transplant
Jan 13, 2012 ABC News First U.S. Patient gets Stem cell trachea Transplant
Jan 12, 2012 New York Times Synthetic Windpipe Is Used to Replace Cancerous One
July 8, 2011 USA Today Patient Gets world’s first artificial trachea
July 11, 2011 Video WGBH A local biotech company grows organs for transplants
Oct 11, 2011 Video New York TV Channel 1 World’s First Artificial Windpipe May Open Door to more procedures
2008-September Claudia Castillo
Jan 21, 2010 Singularity Hub A Tale of Two Windpipes – Determining the Future of Organ Transplants
Nov 19, 2008 BBC Windpipe transplant breakthrough
Nov 19, 2008 Reuters Woman gets first trachea transplant without drugs
Nov 19, 2008 Video Reuters Woman gets first trachea transplant without drugs
Nov 19, 2008 Video UTube-Associated Press Breakthrough Windpipe Transplant uses Stem Cells

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Science Fiction Comes Alive as Researchers Grow Organs in Lab
Courtesy of the Wall Street JournalA person’s heart grows in the womb where its cells receive the right mixtures of oxygen and nutrients and chemicals to grow into a working organ. To duplicate that process in a laboratory, scientists uses a device called a bioreactor, which has various tubes ferrying materials to the heart and whisking away waste products. The lab’s bioreactor-a cylindrical device nearly a foot in diameter-is being designed by Harvard Bioscience.Read More >>

DELIVERING TOOLS TO ACCELERATE RESEARCH PROJECTS AND ADDRESS CLINICAL TREATMENTS HART

Featured Stories

  • Accelerate Research

    Accelerate Research

  • Life-Saving Surgery

    Life-Saving Surgery

  • Russian Transplants

    Russian Transplants

  • Crossing Frontiers

    Crossing Frontiers

Featured Products


  • InBreath Bioreactor


  • 3d Organ Bioreactors


  • Cell Therapy Products


  • ORCA Controller

  In the News

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