ATSMTD's Funding Summary

We invest in translational platforms including stem cell bioengineering and an induced pluripotent stem cell (iPSC) core platform to build capacity in regenerative medicine and to initiate first-in-child UK trials. We aim to pioneer advanced technologies, such as regenerative medicine and the development of new surgical devices, to provide treatment options for children with serious malformations and tissue damage.

To date, ATSMTD have held two internal pump prime rounds (2017/18 and 2019/20); funded two PhD studentships; ran iPSC platform calls that supported the production of iPSC lines for use in research that aim to develop paediatric advanced therapies, and four rounds of the Knowledge Transfer Programme which support post-doctoral early career scientists undertake a placement at an external laboratory. We also have a dedicated clinical research coordinator to support regenerative medicine and clinical research studies that use human tissue obtained from surgeries.

All of these funding opportunities are being held within this current BRC 5 year cycle (2017-2022).

ATSMTD's pump prime awards

Supported by the NIHR GOSH BRC these Pump Prime grants provide an opportunity for researchers, academics and clinicians across a range of disciplines interested in translational research in paediatric rare diseases, to be able to undertake proof-of-principle studies to facilitate the award of further funding. Through this call, we provided funding of up to £50K per project per year to advance development of new treatments and devices to provide therapeutic options for children with congenital malformations and tissue damage.

Craniosynostosis is the premature fusion of bones within the top of the skull at birth. It affects approximately 1 in 2,000 newborn children. Many of these children require surgery to stop the build-up of pressure within the skull, that could damage the brain, and to improve the aesthetic appearance of the head. One surgical approach creates new joints within the skull, however, these can re-fuse, meaning that patients often have to undergo further rounds of surgery. Our aim is to test a new drug treatment that we have discovered which we believe will prevent joint re-fusion following surgery. This will mean that children can spend less time in surgery, which is risky for them and costly to the NHS. It is also likely to improve the aesthetic outcome following surgery. This particular project will test the ability of the drug in cultured cells from patients to prevent tissue at the site of surgery from forming new bone. We will also develop new materials – which can be applied to the surgical wound akin to a plaster – that can deliver the drug only to the site of surgery, thereby avoiding any potential side-effects of the drug.

Gut Motility disorders in children result from a failure of normal formation/function of the nerves and muscles of the gastrointestinal (GI) tract. Enteric neuropathies, the most commonly encountered group of such disorders, specifically refer to defects of the nervous system of the GI tract. They include Hirschsprung disease, Intestinal pseudo-obstruction and a severe form of constipation, slow transit constipation (STC). They are often severe and life threatening if left untreated, but even current treatments, largely limited to surgery, are associated with high morbidity despite considerable clinical expertise. Although it is known that many such conditions are likely to represent birth defects one of the main obstacles towards developing effective treatments has been the determination of the precise defects (e.g. loss of a specific nerve type) that underlie the enteric neuropathy seen in an individual patient.

Acquiring this personalised disease information will be vital to tailor specific therapies. This proposal will build upon the tremendous technological advances (e.g. high resolution manometry), which have allowed the research group to accurately determine which children suffer from neuropathies as opposed to muscle disorders (myopathies). The research study will now use state-of-the-art cell and tissue physiology techniques to accurately determine the nerve defects present in each child suffering from an enteric neuropathy such as STC. The specific novelty here is to use minimally invasive diagnostic tools (endoscopy) that are routinely performed in each patient to obtain tissue samples from the gut. In addition to routine histopathology assessment these samples contain sufficient structures of organised nerve networks (ganglia) to allow the physiology techniques to be performed. The results will inform not only the defects present but also the best approach to treatment and ultimately the potential for regenerative medicine approaches to replace missing or dysfunctional nerves, an area in which the research group have considerable expertise.

Regenerative medicine promises to fully repairing an organ or tissue independently of donor availability. Synchronous progress on stem cell biology, immunological molecular mechanisms, and bioengineering technologies suggests that these ambitious aims might be realistic. The thymus is a primary lymphoid organ essential during foetal and early postnatal life for the establishment of proper immunity against pathogens and induction of self-tolerance, which prevents autoimmunity. Thymic defects may be caused by mutations (FoxN1, Tbx1, Aire, MHC-II & CHD7), chemo-radio therapy, graft-versus-host disease, malnutrition and infections.

In this project we will focus on tissue engineering of the thymus to develop an experimental system to study T lymphocytes development, their interaction with the stromal components and tolerogenic mechanisms that are active in humans. Moreover, during life the thymus undergoes a progressive atrophy. Re-establishing part of its functions might be required to contrast infections, to avoid immune rejections in the context of organ transplantation and also to control autoimmunity.

iPSC Resource Call

This call seeks to support the production of iPSC lines for use in research programmes that aim to develop advanced therapies for childhood diseases. The created iPSC lines will be used to facilitate disease modelling and development of treatments related to childhood diseases, the development of novel cell therapies, and tissue engineering procedures for advanced treatments of malformation and tissue damage.

There have been two calls; one in 2018 and one in 2019.


Hannah Mitchison

Jane Sowden

Jennifer Morgan

Waseem Qasim

Nicola Elvassore

Julien Baruteau

Rick Livesey


Paola Bonfanti

Knowledge Transfer Awards

This programme was launched to support clinical and non-clinical post-doctoral early career scientists to undertake a placement at an external laboratory. The scheme aims to enhance their research skills, facilitate the transfer of key technologies, strengthen collaborations, and develop new partnerships. Placements typically last from 2 to 4 weeks, with a maximum funding allowance of £5,000 per placement.

There have been four rounds:

Anastasia Petrova - hosted by University of California San Francisco, USA, Prof Theodora Mauro

Anastasia’s research focuses on developing novel gene editing tools for a rare genetic blistering disorder called Recessive Dystrophic Epidermolysis Bullosa (RDEB). During this research visit, Anastasia learnt the technique of establishing three-dimensional (3D) skin equivalents from normal and diseased keratinocytes, which can be used to evaluate the efficacy of various reagents in development.

Giovanni Giobbe - hosted by Hubrecht Institute, The Netherlands, Prof Hans Clevers

Giovanni’s research focuses on developing novel applications in tissue engineering, using extracellular matrices and hydrogels. During his secondment in Prof Clevers' group, he performed experiments on human foetal hepatic organoids and liver ductal organoids. He also learnt the isolation protocol from human foetal liver specimens. He was able to successfully replicate this at ICH with his own samples, and further train others in the group, in order to create human hepatocyte models.

Mattia Gerli - hosted by Weill-Cornell Medical College, New York, USA, Dr Shahin Rafii

Mattia’s group uses perfusion decellularization to engineer bioartificial organ using human donor and xenogenic scaffolds, aiming at treating pediatric conditions such as tissue defects and congenital malformations. He was able to further his research into the biology of the amniotic fluid stem cell on his secondment, particularly on their potential for conversion to cardiac progenitors and endothelial cells, as well as set up liver re-endothelialisation experiments with his colleagues at the Weill-Cornell Medical college. He continued these experiments at UCL and shared his knowledge with the PhD students in his research group.

Natalie Chandler - hosted by Li Ka Shing Institute of Health Sciences, Hong Kong, Prof Rossa Chiu

Natalie’s reserach visit allowed her to gain experience of the techniques and bioinformatics tools that her laboratory is employing in order to translate these into a clinical service. She was involved in surrounding non-invasive prenatal diagnosis and optimising current and future assays of cell free fetal DNA, by improving existing assay design procedures with post-doctoral scientists at the Li Ka Shing Institute. In turn, she has trained translational scientists at GOS ICH in how to design these assays, which will be put into standard operating procedures when the test is ready for clinical service.

Alessandro Borghi - hosted by The City College of New York, USA, Dr Alessandra Carriero

Alessandro’s research centres around craniosynostosis, a form of congenital cranial disorder in which one or more cranial sutures (growth seams) fuse before birth, resulting in a deformed head with severe brain and skull growth impairments. This research visit provided him with the opportunity to further study bone fracture mechanics, and he learned robust methods for preparing samples and carrying out fracture toughness tests. His group are planning to perform fracture toughness measurements on these samples once the full laboratory set up has been finalised.

Jennie Chandler - hosted by Yale School of Medicine, USA, Prof Wendy Gilbert (May 2022)

Jennie is interested in kidney diseases that result from the damage or scarring of the blood filtration units, called glomeruli. This scarring is one of the most common causes of kidney failure in children, but despite its prevalence, many of the mechanisms underlying why this scarring happens are still poorly understood. The team recently discovered a new cause for glomerular scarring (Balogh & Chandler et al., 2020; PNAS: 117; 15137-15147), found in a rare childhood syndrome associated with modifications made to the cell’s RNA, called RNA pseudouridylation. Jennie went to Yale University, School of Medicine, to work with Prof Wendy Gilbert, who is an expert in these RNA modifications, to conduct pseudouridylation sequencing on patient cells, to better understand the pathology of this syndrome. On this visit Jennie learnt a highly specialised method to mark the pseudouridines in RNA and how to prepare sequencing libraries, from extracted RNA to barcoded samples ready for sequencing. Jennie has brought this methodology back to GOS ICH, to train others in the group. In the future, this methodology will help BRC researchers to determine better suited therapeutics for end-stage kidney failure and add to our broader understanding of ribosomal and telomere-related diseases

Virginie Mariot - hosted by University of Maryland School of Medicine, USA, Prof Robert J. Bloch

FSHD is the most common muscular dystrophy with 7 cases for 100.000 births and so far there is no curative or preventive treatment. Virginie’s research is focused on developing therapeutic approaches for FSHD through the use of patient derived cells in vitro. During her placement, she learned how to perform xeno-transplantation, which she brought back to GOS ICH to apply this technique in setting up similar experiments in tissue culture.

Giovanni Giobbe – hosted by Cornell University, New York, USA, Prof Shahin Rafii (March 2022)

Giovanni visited Prof Rafii’s group of Cornell University to learn how to culture and characterise reprogrammed vein endothelial cells, the basis for the expansion of this cell type, as well as the differentiation in order to form functional vascular tubes that are able to transport material and fluids during perfusion. This is part of an ongoing novel project investigating the interaction of human liver-specific endothelial cells with human foetal hepatocyte organoids. Liver failure remains a challenging problem and tissue engineered liver could provide an alternative to transplantation but remains hampered by the inability to produce mature universal hepatocytes and tissue specific vascular endothelium.

Giovanni also learned how to integrate human endothelial cells in combination with other cell types, into a microfluidic device that is able to perfuse the 3D culture system, to induce vascularization around the selected cell types. In return, Giovanni taught the Rafii group how to expand and culture human foetal hepatocyte organoids; to use native extracellular matrix hydrogels, and to perform a cell repopulation using perfusion bioreactors.

This visit strengthened the existing collaboration between Cornell university and GOS ICH, opening future possibilities regarding the application of ECM hydrogels with liver-specific endothelial cell types to be transplanted in vivo for therapeutic application.

Benjamin Jevans - hosted by University of Nantes, France, Prof Maxime Mahe (April-May 2022)

The objective of Ben’s visit was to learn how to culture intestinal organoids with a functioning nervous system – a technique developed by a group at the University of Nantes, led by Professor Maxime Mahé. Ben has learned how to grow intestinal organoids and the nerve cells, that are then co-cultured, with the aim to allow further investigation of human gut development, disease and possible treatments. In addition to developing an exciting new collaboration, Ben has brought this technique back to GOS ICH sharing the protocol with other groups interested in intestinal tissue engineering, to better investigate functional innervation of tissue engineered intestinal scaffolds.

Federica Michielin - hosted by Boston Children's Hospital, Harvard, USA, Prof Carla Kim (June 2022)

Federica visited Prof Kim’s lab at Boston Children’s Hospital, to learn how to grow lung organoids, useful to model the late stages of human lung development. This allows investigating pathogenesis mechanisms of lung hypoplasia (underdeveloped lung due to congenital malformation which may lead to neonatal death). Federica has brought this technique back to GOS ICH and will train lab members on the culture and differentiation of alveolar progenitor organoids.

Alexandra Kreins - visiting Leiden University, Netherlands, Prof Frank Staal (pending in Sept 2022)

Non-Clinical PhD Studentships

The NIHR GOSH BRC funds early translational (experimental medicine) research, which aims to translate discoveries from basic/discovery science into clinical research and through to patient benefit and economic benefit. The BRC ‘Advanced Treatments for Structural Malformation and Tissue Damage’ theme aims to pioneer advanced treatments for children with congenital malformations and tissue damage, for whom there are currently few or no therapeutic options. The theme brings together specialists in paediatric surgery, developmental and stem cell biology, regenerative medicine, tissue engineering and device development to build a unique expertise to facilitate the development of innovative treatments based on successful proof-of-concept.

NIHR GOSH BRC funded two 3-year PhD Studentships within the Developmental Biology and Cancer programme at UCL GOS Institute of Child Health and within the ATSMTD theme. The projects started in October 2020 and were awarded to:

Ioakeim Ampartzidis: Tissue engineering a patch to repair neural tube damage during in utero surgery for spina bifida

David Martos Ruiz: Tissue engineering a retinal patch using stem cell-derived photoreceptors to treat retinal dystrophy

Research coordinator support

The ATSMTD theme has a dedicated research coordinator who provides support for tissue engineering and regenerative medicine studies. Specific areas supported by the coordinator include:

  • Patient-facing: consent discussions with patients, receiving consent
  • Study-related: screening, coordinating study visits, liaising with research team members, consultants & nurses in wards/theatre, site file management, tissue sample collection
  • Admin: BRC quarterly reports, grant balance updates, etc.
  • Ethics: Assist in the preparation of study documents for regulatory admissions

Our portfolio includes a wide range of specialities, including studies in craniofacial, gastrointestinal, ophthalmology & audiology, renal & urology, and immunology.

We support a wide range of studies that utilise leftover tissue from surgeries to understand how diseases that result in congenital conditions work and focus on developing treatments through tissue engineering approaches. These studies cover a wide range of structural malformations, including those that affect the intestine, oesophagus, gut, liver, and muscle.

For example, we support Craniofacial Group at GOSH and GOS ICH, contributing to FaceValue objectives. The group aims to develop novel techniques and devices to improve quality of life for children born with conditions that affect their head and/or face.

2020 - New Projects Funding Call

This call aims to fund a number of new translational research ideas at GOSH/ICH across a wide range of areas mapping to the broad BRC objectives. The call is primarily focused at early career researchers and the aim is for the new research ideas to help shape the BRC’s future strategic direction. There is a total of £300,000 available with around £30,000 available per one-year award.

Internal GOSH and ICH applicants only. The lead applicant must hold a substantive contract with one of the organisations (staff or student contract).

2020 New Projects Funding Call - ATSMTD awardees:

At birth, the baby skull is formed by hard bone parts that are joined by soft tissue called sutures. These sutures play a fundamental role in allowing the baby natural birth and head growth in the first few years. By the time the baby is two, the head has quadrupled in size. Sutures become bone when the child grows older. In babies affected by craniosynostosis (one in 2000 births), one or more of the skull sutures harden prematurely. If this happens, the head develops abnormally and the brain growth is restricted, thus leading to eyesight, earing and breathing problems and developmental delays.

Corrective surgery is performed by cutting and reshaping cranial bones during an extensive procedure which requires long hospital recovery. Surgeons at GOSH have pioneered a new technique, where only a few small cuts are performed on the skull and spring-like-devices (distractors) are temporarily inserted to widen the skull and normalise the shape. This new operation has proved effective in shortening operative time and ensuring a speedy recovery. Such surgery is currently only suitable for selected types of craniosynostosis. Patients affected by unicoronal craniosynostosis (UC) require complex 3D reshaping which cannot be achieved by the current devices.

Metal additive manufacturing (AM) allows production of complex shapes without the limitation of standard manufacturing methods. In this project, a new device for UC correction will be designed and manufactured in nitinol (a special nickel titanium alloy which can be programmed to produce specific distraction patterns) by means of AM, i.e. by depositing layers of metal powder. Computer simulations replicating device insertion on realistic patient skulls, extracted from computed tomography, will be used to design a novel distractor able to perform head reshaping and achieving normalisation. The final prototype will be manufactured using nitinol AM and tested in-vitro for validation.

The correct functioning of the gut depends on the movement of the gut wall which allows food to move along the gut. This functional movement is called "motility". Motility in the gut is caused by the actions of a number of different cell types including nerve cells, muscles and a cell type called interstitial cells of Cajal, or ICC. When there is an issue with any of these cells this results in diseases called "gut motility disorders." Unfortunately, there are no cures for these diseases. Due to this, treatment remains a challenge and patients often have surgery to remove large pieces of gut. This can cause significant problems, as patients have to live with long-term, life-altering symptoms. Therefore, new treatments for these diseases are vital.

Although we do not know the exact cause of these diseases, studies have found less ICC numbers in tissues taken from patients suffering from motility disorders. ICC are found all along the bowel in networks. They cause the muscle of the gut to contract and relax, in rhythm. Due to this rhythm, ICC are called "pacemakers" of the gut. Previous research in mice has shown how ICC develop and how they function. This has also shown that if that if ICC are lost this leads to problems in motility. However, little is known about ICC development, function and loss in the human gut.

Therefore, this proposal aims to develop new tools to investigate human ICC. To do this, we will tag human stem cells with fluorescent markers and then use a system which can grow human gut tissue in a dish. Using this approach, we will be able to grow human gut tissue containing our tagged ICC which will allow us to determine how these cells develop and begin to function.

Our spinal cord is made up of long nerves which connect our brain to our muscles and organs. These nerves are damaged in babies who are born with spina bifida, which is a severe birth defect in which the spinal cord develops unprotected outside of the body. The quality of life of individuals who have spina bifida can be improved by performing surgery inside the womb to protect their spinal cord before they are born. Unfortunately, this surgery does not fully restore the function of their nerves, so they are still often born unable to use their legs or control their bowel and bladder. Our research hopes to improve outcomes for these individuals by delivering treatments, at or before the time of surgery, which replace or replenish their damaged nerves. To do that, we first of all need to know if all the important nerves typically found in the spinal cord are also present in spina bifida. Previous findings suggest they might not be. We know that the tube-like shape of the spinal cord, covered by skin above it, normally instructs key nerve types to form in the correct place. This shape is lost in spines with spina bifida, and they are not covered by skin. Our research will show whether spinal cord shape differences predictably stop some nerves developing correctly and we will create a stem cell model in which we can test advanced therapies to rescue them. In the long run we hope to develop stem cell treatments which can be combined with minimally invasive fetal surgery to fully restore spinal nerve function in babies who have spina bifida.

Craniosynostosis (CS) is a birth defect in which fibrous joints (sutures) between two or more bones of the skull prematurely fuse. CS (1 in 2,500 births) is classified as part of a genetically defined syndrome or nonsyndromic. Sagittal CS (SCS) is the most common type, accounting for between 40% and 58% of non-syndromic cases.

CS results in abnormal head shape at birth and restricts brain development leading to a build-up of pressure inside skull. If not surgically treated, the pressure may result in visual and neurological harm. Spring assisted cranial expansion is a surgical approach used to treat CS patients. It involves removing a small piece of skull bone, minimised cuts on the skull and temporary insertion of springs to normalise the head shape. However, accurate prediction of patients final head shape remains a challenge for surgeons as limited information is available on paediatric skull properties.

Research from our group has shown that achieving optimal correction of skull deformity in SCS patients (<1 year old) is not related to age and depends on skull bone properties and structure. Hence, mandating the need for individualised approach for surgical success. Using a pre-clinical bone testing device we were successful in identifying different material properties and macrostructure in SCS skull bone samples. In this project, we would like to use a clinical version of the same device (EU approved medical device) which is a portable handheld impact microindenter to examine cranial samples that would be discarded during routine surgery. The aim is to investigate: (1) the material properties of cranial bone in CS patients; (2) if the material properties would correlate with the surgical outcome; and 3) the safety application of this device on the pediatric patients. Ultimately, this study will help surgeons to develop new surgeries, reduce variability, and provide personalised care.

2022 - Translational Researcher Salary Call

NIHR GOSH BRC is currently in its final year of funding in its third term, and we have around £150,000 available to provide up to six months’ salary or stipend to support staff or students who are undertaking experimental medicine research aimed at improving outcomes for children and young people with rare or complex diseases. The purpose of the call is to maximise outputs from existing translational research projects, retain exceptional translational researchers within GOSH/ICH and/or to facilitate early initiation of new projects where future funding has already been secured/sought.

Applications are welcome from all staff employed within GOSH/ICH, including clinicians, non-clinical, nursing and AHP staff and any others not mentioned here. NIHR funding is formally not allowed to support any research using animals; therefore, no animal work is permitted. Furthermore, no staff/student recruitment will be allowed as part of this call.

2022 Translational Researcher Salary Call - ATSMTD awardees:

Norrie disease is a rare genetic condition that mostly affects boys. They are born blind and with normal hearing. Their hearing gets worse gradually . Our research is aimed at slowing or preventing the hearing loss and thus the dual sensory deprivation that seriously holds these patients back from interacting and communicating with others.

By looking into Norrie patients and disease models our team found out the changes in the cochlea, the coiled structure in the inner ear that detects sound. We found that the blood vessels in the cochlea were not normal and hair cells (sound sensing cells) died.

Norrie disease is caused by a mutation of a single gene NDP. We are now investigating if treatment with an Adeno-associated virus (AAV), engineered to carry a replacement, healthy, copy of NDP can prevent the abnormal changes in the cochlea and the hearing loss. Such gene therapy constructs will be tested in cells and organoids, grown in the lab. Based on the results of this project, we will test the new gene therapy in future pre-clinical studies for their ability to prevent hearing loss.

Congenital Diaphragmatic Hernia (CDH) is a life-threatening disease, in which the diaphragm fails to close during prenatal development and thereby the contents of the abdomen migrate into the chest cavity through this hole, altering normal lung development and function. In Europe, 2.3 per every 10,000 infants are born with CDH, accounting for approximately 8% of the most common severe birth defects.

Children with CDH have severe respiratory distress and mortality is above 30%. For the most severe cases, prenatal intervention involves the placement of a balloon in the airway which increases the pressure in the lung to reduce the compression of the abdominal organs herniated through the diaphragmatic defects. To date however, it is unclear whether the lungs are poorly functioning because of an intrinsic lung developmental problem or because of mechanical compression from the herniated tissue.

This project aims at understanding the role of mechanical compression experienced by CDH fetuses on lung development, offering new information on the disease, and identifying new clinically-relevant molecular targets, that will potentially allow rescuing lung development, likely in association with currently available surgical procedures.

Improving or rescuing lung growth will both improve mortality and reduce respiratory distress in CDH patients.

The liver produces proteins that are involved in key metabolic processes needed for interconversion of biochemicals in the body and which remove harmful toxins from the blood. Inherited liver disease or liver failure are life threatening conditions. However, liver transplantation is far from an ideal therapy due to shortage of donor organs, the high risk of the surgery, especially in babies and children, the life-long problem of rejection and the consequent need for immunosuppression to prevent this. There is also a higher risk of developing cancer and/or kidney failure.

Cell therapy is an attractive other option to whole organ transplantation as a large number of metabolically active cells can be provided without the need for supporting tissues. However, liver cell therapy has yet to impact on clinical care due to the difficulty in producing, delivering and maintaining a large number of functional cells.

Human pluripotent stem cells (hPSCs) are cells with an unlimited ability for self-renewal, which can be developed into hepatocytes, the mature liver cells. Recently, we developed a novel approach to generate stable spheres of mature liver cells (3D Hepatospheres) from hPSCs under the stringent conditions required for human cell therapies.

The current project will further develop methods of cell delivery of the 3D Hepatospheres for liver disease by developing a methodology to encase cells in a jelly-like material that shields the cells from the recipient immune system. This could provide a universal cell source for cell transplantation as it avoids the need for an immunosuppression regimen or an immunological matched donor. In addition, we will optimise a cryopreservation method to which would allow cells to be stored at very low temperatures and then thawed for use. This will be an important step to make encapsulated 3D Hepatospheres an off-the-shelf cell-based therapy for a range of liver disease.

As a complementary approach, we generated 3D-Heps from patients with Non-Ketotic Hyperglycinemia, a life-limiting genetic disorder that involves abnormal liver metabolism. These 3D-Heps can be used to test gene therapy vectors as a precursor to use in clinical studies.

Hirschsprung disease is a life-threatening disease whereby babies are born with no nervous system in a portion of their gut. Unfortunately, the only current treatment for this disease is a complicated surgery to remove the affected region of gut. However, this current treatment option often leads to lifelong issues so there is a desperate need for new ways of treating these children.

In this project, we want to use stem cells to try and replace the lost nervous system in these children’s guts. To do this we will first create donor gut nervous system cells in a dish. We will then transplant these cells into small pieces of bowel which have been removed at surgery and would otherwise be gotten rid of. The transplanted pieces of gut will then be kept in an incubator for 3 weeks. After this we will check to see if our transplanted stem cells can rescue the small pieces of bowel.