The Use of Stem Cells in the Surgical Treatment of Cleft Palate

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The Use of Stem Cells in the Surgical Treatment of Cleft Palate

   

Caroline C. McCall1 and Vincent S. Gallicchio2*

1Department of Biological Sciences College of Science Clemson University Clemson, SC 29636, USA

2Department of Biological Sciences College of Science Clemson University 122 Long Hall Clemson, SC 29636, USA

*Corresponding author: Dr. Vincent S. Gallicchio, Department of Biological Sciences College of Science Clemson University 122 Long Hall Clemson, SC 29636, USA

Citation: McCall CC, Gallicchio VS. (2022) The Use of Stem Cells in the Surgical Treatment of Cleft Palate. J Stem Cell Res. 3(3):1-11.

Received: August 6,  2022 | Published: August 29, 2022

Copyright© 2022 by McCall CC. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

DOI:  https://doi.org/10.52793/JSCR.2021.3(3)-41

Abstract

Mesenchymal stem cells, pluripotent and differentiable cells found naturally within bone marrow, adipose tissue, the blood of the umbilical cord, and dental pulp have the capability to transform the field of oral surgery. With the capability to differentiate into different types of tissue, stem cells are currently being studied as an alternative to autologous bone grafting for treatment of cleft palate in young children. The long-standing treatment of autologous bone-grafting, while very effective, has many risks associated with it such as graft rejection, post-operative morbidity, and long recovery time. The harvesting and transplantation of stem cells using bio-compatible scaffolding that will differentiate and form new bone tissue is the future of valvuloplasty protocol in the field of oral surgery. This paper will investigate the way in which this treatment will be performed, the advantages and risks of stem cell therapy, the future applications, as well as the issue of global accessibility to innovative treatment such as this. 

Keywords

Stem Cells; Therapy; Cleft Palate

Background

Affecting about 1 in every 1,700 babies in the United States, cleft palate consistently remains one of the most common birth defects in the country(along with congenital heart defects, spina bifida, and Down Syndrome) and present unique and multidisciplinary challenges for dentists, plastic surgeons, pediatricians, and oral surgeons [1]. Cleft palate is defined as an opening or split in the upper roof or palate of the mouth, separating the oral and nasal cavities, sometimes in conjunction with cleft lip. This fusion of tissue normally occurs in the second or third month of pregnancy and improper fusion could be due to a variety of environmental, as well as genetic, factors[2]. Cleft palate can lead to complications for the patient such as difficulty breathing, poor feeding ability, nasal-forward speaking voice, poor tooth development, and ear infections. Therefore, it is important to treat individuals born with cleft palate from an early agedue so as to not hinder their speech and eating development, preferably during the mixed dentition phase to avoid tooth decay caused by the cleft palate [3]. It is also favorable to begin treatment at a young age due to the long duration of multi-step treatment that must be conducted to safely and effectively engineer the palate. Despite cleft palate being so commonly observed by surgeons and physicians, no standard protocol or method of treatment has been developed [4]. It is still highly variable among surgeons. However, the large majority of cleft palate patients are treated by performance of autologous bone grafting. This autologous bone (bone donated from a different location of the recipient’s body) is typically relocated from the iliac crest of the hip boneto the palate of the patient to close the gap in the roof of the mouth and fuse it into one singular component, thereby relieving the patient of breathing and feeding difficulties. A variety of procedures such as alveoloplasties, gingivoperiosteoplasties, and cheiloplasties are used to correct palatal clefts with the least amount of damage and shortest recovery period (Figure 1).

Figure 1: Palatogenesis: the development of the palatal shelves during fetal development. Occurring between weeks 8-12, the palatal shelves begin by growing in a downward direction before turning upward and fusing together to separate the nasal and oral cavities. This fusion does not properly occur for children with cleft palate [4].

A new technique to repair clefts in the palate involves implementation of stem-cell regenerative procedures into the existing cleft palate surgical treatment to reduce procedural risks, as well as the healing time for patients after cleft palate surgical treatment. The main types of mesenchymal stem cells currently being used in engineered palates are stem cells derived from the umbilical cord blood, adipocytes, dental pulp, and bone marrow. This paper will focus on stem cells from both bone marrow and umbilical cord blood. Both types of stem cells are currently being utilized in treatment. While stem cell treatment is still regarded as a rather controversial treatment option given the risks of stem cell transplantation and the lack of long-term clinical research, the potential for stem cell regenerative treatment in the field of oral surgery is great (Figure 2).

Figure 2: Application and Placement of stem cells in conjunction with bone scaffolds for orofacial deformities or disease. The placement of the stem cell transplantation for cleft palate can be seen on the far right, however there are many other applications and capabilities for these stem cells in oral surgery [5].

Alveoloplasty Surgical Protocol Using Stem Cells

An alveoloplasty surgical procedure is one in which the size or shape of the alveolar bone is altered or manipulated. For treatment of cleft palate, a primary alveoloplasty procedure is typically performed prior to the patient turning two years of age. Any alveoloplasty procedure performed after that time would be considered a secondary alveoloplasty [3]. Alveoloplasty procedures have been performed on patients to treat cleft palate for over 170 years, with the most common method being Boyne’s Method. Boyne’s Method involves an autologous bone graft from either the iliac crest or, in the case of larger grafts, ribs of the patient. The bone graft is harvested in the desired shape and size, and then transferred to the site to correct the alveolar process. However, the use of autologous bone grafting can lead to complications and health risks, such as infection, prolonged drainage and pain, sensory loss, long-time hospitalization, and high cost [6]. Especially in pediatric patients, this invasive procedure requires a large availability of bone for harvesting. This is rather limited in young patients. [7].Stem cells from autologous bone marrow or from store umbilical cord blood can be used as an alternative method to autologous bone grafting as an effort to avoid the aforementioned risks. With the ability to regenerate various tissues, the method of transferring stem cells from bone marrow, dental pulp, or umbilical cord blood to the cleft palate via scaffolds could prove to provide a safer and more pleasant procedure for the patient. The purpose of a scaffold is to act as a sort of framework at the site stem cells transplantation, as well as allow the new tissue to be vascularized, integrate with the existing tissue, and survive as it is being generated [8]. It is important to note that these scaffolds must be biocompatible, as well as have a rate of absorption comparable to the bone growth rate to avoid immune-rejection or transplant-site morbidity [7]. Synthetic bone grafting also relies on its osteoconductive and osteoinductive capabilities. The ability of the stem cells to move across the scaffold to attach, migrate, and grow to regenerate the bone tissue is known as osteoconduction [9].  Osteoinduction is the process in which the bone-forming stem cells stimulate osteogenesis (formation of bone) through recruitment of cells [10]. Both are crucial in the success of the regenerated tissue after being transplanted to the palate.

Despite the novelty of this method of oral surgical cleft palate rehabilitation, these cells in conjunction with a suitable scaffold show great promise in their capability to regenerate bone tissue. This surgical protocol has also proven to reduce the overall time of treatment, “decrease the inflammatory process”, and improve the appearance of visible scarring visible on the patient [11]. The largest obstacle for this method is its cost-effectiveness. Currently, it is generally more expensive to transfer multipotent stem cells in conjunction with a scaffold than to perform an autologous bone graft [12], however the cost has decreased over time and is predicted to keep decreasing as more regenerative techniques are established. 

Umbilical vs. Bone Marrow Mesenchymal Stem Cells

Stem cells are a fundamental part of human biology and act as a starting point for all organs and tissues of the body. These stem cells can either exist only during human development (known as embryonic stem cells) or can develop later in fetal development and remain in the body for life, such as the case for mesenchymal stem cells found in bone marrow[13]. In the treatment of cleft palate, the two main sources ofstem cells are bone marrow and the umbilical cord. Both are considered human mesenchymal stem cells. Mesenchymal stem cells (MSC’s) are present in all tissue types and have the ability to differentiate into a wide variety of body tissues, including cardiac muscle, cartilage, and, in the case of cleft palate, bone. With easy accessibility and isolation, MSC’s have been identified as prime candidates for autologous and allogenic transplants over other types of stem cells such as embryonic stem cells. While most of clinical research that has been conducted uses MSC’s sourced from bone marrow, recent use involving stem cells sourced from the umbilical cord could prove to widen the application of stem cells globally in a clinical sense.

Bone marrow is a very complex body tissue system, consisting of many different specialized cells with unique functions. A network of connective tissue known as the marrow stroma includes of undifferentiated cells that do not perform hematopoietic functions and have the capability to form a range of different phenotypes. The mesenchymal stem cells make up a very small percentage of the nucleated cells in this bone marrow stromal network. The cells within the stroma have been defined as mesenchymal stem cells because of their ability to proliferate and differentiate. Bone marrow mesenchymal cells, while widely accessible and available, do have their limitations regarding “the high degree of viral exposure” that they face, the slowing of proliferation capabilities as the individual ages, and the invasive, painful means to obtain bone marrow samples. Therefore, the ability to source stem cells from a different location could have clinical benefits [14] (Figure 3).

Figure 3: Anatomy of bone marrow, showing the stromal complex within the bone marrow containing mesenchymal stem cells. These stem cells have a great capability to differentiate into osteoblasts, adipocytes, chondrocytes, as well as other cell types [15].

The anatomy of the human umbilical cord includes two arteries and one vein surrounded by a mucoid connective tissue called “Wharton’s jelly”. After birth, the blood within the umbilical cord “contains a rich source of hematopoietic stem and progenitor cells” and can be obtained in a painless and ethical manner for the both the mother and child. Primitive stromal cell can be obtained from Wharton’s jelly and differentiated [14]. Sourcing stem cells from the blood of the umbilical cord has grown increasingly more popular due to the low-cost and ethical means of harvesting. Unlike embryonic stem cells, no damage is done to the child when the umbilical cord blood is banked or used later for stem cell harvesting [16].