Cell Therapy
Cleft Lip and Cleft Palate
Background
Cleft lip and cleft palate are openings or splits in the upper lip, the roof of the mouth (palate) or both. Cleft lip and cleft palate result when facial structures that are developing in an unborn baby don’t close completely1.
Cleft palate is the second most common birth defect caused by disturbed embryonic development of soft and hard tissues around the oral cavity and face area, resulting in most cases of severe limitations with chewing, swallowing, and talking as well as problems of insufficient space for teeth, proper breathing, and self-esteem problems as a consequence of facial appearance. Cleft lip and cleft palate most commonly occur as isolated birth defects but are also associated with many inherited genetic conditions or syndromes. The cause is unknown in most cases1. Risk factors include smoking during pregnancy, diabetes, obesity, an older mother, and certain medications (such as some used to treat seizures)1.
A cleft lip or palate can often be successfully treated with surgery.
However, the cleft left lip and cleft palate are considered as a challenge for pediatric plastic surgeons. There is still a general lack of a standard protocol and patients often require multiple surgical interventions during their lifetime. There are numerous surgical approaches to the repair of a cleft defect, depending upon the type of cleft and other health problems. The use of stem cells and regenerative medicine open new possibilities of improving the final results in different pathways2. The most widely used type of grafting in bone regeneration defects is the use of autogenous bone 3. However, the availability of autogenous bone is limited and is not free, of drawbacks especially in pediatric patients where the availability for harvesting bone may be limited and thus may not be the ideal graft for bone reconstruction.
There are some studies that have focused on the application on tissue engineering to the regeneration of the lip4,5 and a few have reported significant advances to offer real clinical solutions.
Ideas to use stem cells and blood from the umbilical cord and also blood from placenta are discussed to improve surgical results. Maternal stem cells, umbilical cord tissue derived mesenchymal stem cells and umbilical cord blood stem cells are both available in relatively large quantities from morally acceptable sources with collection using no painful or invasive techniques. Since the age of these stem cells are the age of the new born, umbilical cord stem cells have a greater potential to regenerate the organism. Immediately after delivery, a sample of the infant´s umbilical cord blood or cord tissue is collected, to isolate stem cells, which are processed and frozen to preserve them for later use.
Clinical studies:
A technique using umbilical cord blood stem cells and placenta blood could be a promising new approach for repair of cleft palate in infants reports, Mazzetti and colleagues, in The Journal of Craniofacial Surgery, 2018 6.
Nine patients with cleft lip and palate were operated and had stem cells from umbilical cord and placenta blood injected into the bone and soft tissue as part of reconstitutive surgery when the infant was a few months old. The stem cells activity into soft tissue and bone were evaluated and the stem cell procedure provides good results in growing new bone to close the upper jaw cleft and may avoid the need for later bone graft surgery, according to the case report by Alejandro Garcia Botero. Follow-up confirmed formation of new bone to clos the cleft palate, providing good position and support for normal eruption of the teeth. Imaging scans when the patient was five years old showed good thickness of the upper jawbone in the area where the cleft had been.
The article is available here
A major potential advantage of the stem cell procedure is avoiding the need for later bone grafting surgery, currently the standard technique for closing the cleft.
This procedure uses bone taken from elsewhere in the child´s body, typically the hip. Bone grafting has potential complications and subjects the child to more additional surgeries.
The study is the first to use stem cells as part of primary surgery to repair cleft palate in an infant. The researchers emphasize the need for further studies evaluating their stem cell technique in a large number of patients. Examples of other clinical trials are NCT01932164 and NCT03563495. Results from these studies can be found at clinicaltrials.gov.
References
- Watkins, S. E., Meyer, R. E., Strauss, R. P. & Aylsworth, A. S. Classification, epidemiology, and genetics of orofacial clefts. Clin Plast Surg 41, 149-163, doi:10.1016/j.cps.2013.12.003 (2014).
- de Ladeira, P. R. & Alonso, N. Protocols in cleft lip and palate treatment: systematic review. Plast Surg Int 2012, 562892, doi:10.1155/2012/562892 (2012).
- Berger, M. et al. A concept for scaffold-based tissue engineering in alveolar cleft osteoplasty. J Craniomaxillofac Surg 43, 830-836, doi:10.1016/j.jcms.2015.04.023 (2015).
- Raposo-Amaral, C. E. et al. Alveolar osseous defect in rat for cell therapy: preliminary report. Acta Cir Bras 25, 313-317, doi:10.1590/s0102-86502010000400002 (2010).
- Tanikawa, D. Y., Aguena, M., Bueno, D. F., Passos-Bueno, M. R. & Alonso, N. Fat grafts supplemented with adipose-derived stromal cells in the rehabilitation of patients with craniofacial microsomia. Plast Reconstr Surg 132, 141-152, doi:10.1097/PRS.0b013e3182910a82 (2013).
- Mazzetti, M. P. V. et al. Importance of Stem Cell Transplantation in Cleft Lip and Palate Surgical Treatment Protocol. J Craniofac Surg 29, 1445-1451, doi:10.1097/SCS.0000000000004766 (2018).
