Key points:
- A new approach to repairing peripheral nerves using gingiva-derived mesenchymal stem cells and a biological scaffold for facial injury.
- Traditional approach is nerve autograft
- Here, gingiva-derived stem cells are laid in collagen hydrogel on a scaffold, leading to the formation of Schwann cells that produce growth factors.
- Results similar to autograft, without the loss of nerve linked to the exograft.
- The mechanism of action is the migration of circulating stem cells into the scaffold.
- Increasing the number of circulating stem cells, which can help repair brain and spinal cord injury, could lead to similar results or support this treatment.
Story
Since the discovery of the nervous system as we know it today, by Ramón y Cajal, the traditional view is that the brain and nervous system do not regenerate.
But discoveries at the turn of the century revealed that:
- Bone marrow stem cell cells can transform into brain cells
- The brain has its own resident neuronal stem cells, these cells are responsible for significant repair in the brain
- Other types of stem cells, like hair follicle stem cells, dental pulp stem cells, and gingival stem cells can also regenerate the brain and peripheral nerves
The traditional treatment for the loss of facial nerves is the surgical removal of a nerve in the leg of arm of a patient and its transplant in the face. Aside from not always working very well, it leaves the patient with deficiencies where the nerve was excised.
A novel alternative approach is to extract gingival stem cells, embed them into a collagen hydrogel which is inserted into a biological scaffold covering the area where the nerve regrowth is needed. This approach leads to the formation of a new nerve, without the loss of nerve sensation elsewhere in the body.
In this approach, the key mechanism of action is the migration of circulating stem cells into the scaffold, attracted by the growth factors secreted by the gingival stem cells. (1,2,3)
Simply stimulating the release of stem cells from the bone marrow, a process referred to as “Endogenous Stem Cell Mobilization”, using Granulocyte-Colony Stimulating Factor (G-CSF), was documented to help regenerate nerve to the point of helping to even repair spinal cord lesion, which is considered incurable (4,5,6).
Unfortunately, G-CSF can lead to severe side effects in humans and therefore cannot be used for treatments. As an alternative, plant extracts have been documented to also trigger Endogenous Stem Cell Mobilization. Their effect is much milder, but their long-term use can also lead to significant repair of the nervous system (7).
Endogenous Stem Cell Mobilization
Bone marrow stem cells (BMSC) have been traditionally known to be precursors to blood cells and to have little ability to transform into other type of cells. What has led to an extraordinary expansion in the field of stem cell research is the discovery that BMSC not only have the ability of transforming into virtually any other types of cells in the body, but they do so every day as part of the body’s repair system.
The key parameter is the number of circulating stem cells. More stem cells in circulation means that more stem cells are available to participate to the process of tissue repair. The traditional way of increasing the number of circulating stem cells is through an injection of stem cells, isolated from an umbilical cord or from one’s own body (e.g. blood, bone marrow, fat tissue).
A novel approach is to stimulate the release of stem cells from one’s own bone marrow, a process called Endogenous Stem Cell Mobilization (ESCM). ESCM has been documented to improve a long list of health problems. Unfortunately, the use of pharmaceutical compounds known to trigger ESCM in humans, such as Granulocyte Colony-Stimulating Factor (G-SCF), is limited by the toxicity of these compounds. Recently, plant extracts have been documented to have the ability to stimulate ESCM. These plants have been coined “Stem Cell Enhancers”. Stemregen is a blend of the most potent Stem Cell Enhancers documented so far.
References
- Saez DM, Sasaki RT, Martins DO, Chacur M, Kerkis I, da Silva MCP. Rat facial nerve regeneration with Human Immature dental pulp stem cells. Cell Transplant. 2019 Dec;28(12):1573-1584. https://pubmed.ncbi.nlm.nih.gov/31462071/
- Jia H, Wang Y, Chen J, Li JP, Han HQ, Tong XJ, He ZY, Ma WZ. Combination of BMSCs-laden acellular nerve xenografts transplantation and G-CSF administration promotes sciatic nerve regeneration. Synapse. 2019 Jul;73(7):e22093. https://pubmed.ncbi.nlm.nih.gov/30761618/
- Pan HC, Wu HT, Cheng FC, Chen CH, Sheu ML, Chen CJ. Potentiation of angiogenesis and regeneration by G-CSF after sciatic nerve crush injury. Biochem Biophys Res Commun. 2009 Apr 24;382(1):177-82. https://pubmed.ncbi.nlm.nih.gov/19275877/
- Li J, Chen L, Chen Q, Hu D, Lin J. Effect of granulocyte colony-stimulating factor mobilizing bone marrow mesenchymal stem cells homing to injury sites in spinal cord injury of rats. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2019 Jan 15;33(1):93-100. https://pubmed.ncbi.nlm.nih.gov/30644268/
- Qiu X, Ping S, Kyle M, Chin L, Zhao LR. SCF + G-CSF treatment in the chronic phase of severe TBI enhances axonal sprouting in the spinal cord and synaptic pruning in the hippocampus. Acta Neuropathol Commun. 2021 Apr 8;9(1):63. https://pubmed.ncbi.nlm.nih.gov/33832542/
- Aschauer-Wallner S, Leis S, Bogdahn U, Johannesen S, Couillard-Despres S, Aigner L. Granulocyte colony-stimulating factor in traumatic spinal cord injury. Drug Discov Today. 2021 Jul;26(7):1642-1655. https://pubmed.ncbi.nlm.nih.gov/33781952/
Drapeau C, Eufemio G, Mazzoni P, RToth GD, Stranberg S. The therapeutic potential of stimulating endogenous stem cell mobilization. In: Tissue Regeneration, Eds. Jamie Davies, From Basic Biology to Clinical Application, Prof. Jamie Davies (Ed.), 2012; Chapter 8: 167-202. ISBN: 978-953-51-0387-5, InTech, Available from: https://cdn.intechopen.com/pdfs-wm/34637.pdf
