Adult stem cells for glaucoma and optic neuropathy or will be achieved

Copyright © iCell Bioscience Inc, Shanghai 2018-2019

Glaucoma is a serious irreversible blinding eye disease worldwide. It is the main cause of vision loss after cataract. At present, glaucoma has more than 100 million people worldwide. Retinal ganglion cell (RGC) degeneration is a common cause of glaucoma and optic neuropathy, which is the main cause of irreversible blindness and visual impairment. Lowering intraocular pressure can slow the progression of glaucoma in some patients, but there is currently no effective treatment for optic neuropathy.

Degenerative retinal ganglion cells in glaucoma cannot be repaired, and the regenerative potential of human retina is limited. Cell replacement and neuroprotection are the main strategies for the treatment of glaucoma and optic neuropathy. Replacing diseased or degraded cells with stem cell-derived retinal ganglion cells can provide effective treatment.

Currently, human adult stem cells have nine clinical trials for glaucoma and optic nerve diseases. Treatment of glaucoma and optic neuropathy in human adult stem cells may be achievable in the near future.

Adult stem cells are quiescent, undifferentiated cells found in fully developed tissues with the ability to self-renew and differentiate into mature cells. Adult stem cells can be conveniently isolated from accessible tissues, including bone marrow, peripheral blood, adipose tissue and teeth. Different types of adult stem cells, such as hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), and neural stem cells, can be identified based on their lineage. Although adult stem cells maintain the homeostasis of adult tissues through cell replacement and tissue regeneration, they can also modulate the microenvironment in host tissues and protect RGCs from denaturation.

The neuroprotective effects of adult stem cells on RGC degeneration are mainly studied in mesenchymal stem cell MSCs. Different sources of MSCs, including rat and mouse bone marrow, adipose tissue, human chorionic lining and rat pulp, have been shown to enhance RGC survival after optic nerve injury. The mechanism of neuroprotection of mesenchymal stem cells can regulate the plasticity of damaged host tissues, secrete neurotrophic and growth-promoting growth factors, restore synaptic transmission, integrate into existing neural and synaptic networks, and reconstruct functional afferents. And outgoing connections.

The study found that human periodontal ligament stem cells (PDLSCs) after vitreous transplantation can survive and migrate to the RGC layer and even the optic nerve. Cell-cell interactions are a key condition for protecting RGCs from degeneration, as RGC survival is increased by the way in which human PDLSC-retinal explants are co-cultured.

In addition, human periodontal ligament stem cells highly express some neurotrophic factors such as BDNF, CNTF, GDNF and NT-3, which are essential neurotrophic factors for enhancing RGC survival and axonal regeneration. Our human PDLSCs and other reported studies suggest that future MSCs can be used to treat glaucoma and optic neuropathy.

Human adult stem cells for retinal ganglion cell regeneration: The basis of cell replacement therapy is the ability to regenerate new retinal ganglion cells from stem cells to replace damaged retinal ganglion cells in glaucoma or optic neuropathy. Pluripotent stem cells, including embryonic stem cells (ESCs) and induced pluripotent stem cells (ipsC), have been studied because they can differentiate into retinal lineages. Although adult stem cells are considered to be tissue-specific and have limited differentiation capabilities, more and more studies have reported that adult stem cells can produce completely different lineages.

The pluripotent subpopulation can be found in human PDLSC. These pluripotent adult stem cells are neural crest stem cells that are present in neural crest-derived adult tissues. They can form teratomas with tissues from three embryonic germ layers (endoderm, mesoderm and ectoderm) in immunodeficient mice and can be induced into neuronal lineages, meaning that pluripotent adult stem cells can be derived from humans. The need to separate and enrich in adult tissues without the need for reprogramming. The use of pluripotent adult stem cells can increase the efficiency of RGC production.

In addition to ESC and ipsC, adult stem cells can also be used to produce RGCs for the treatment of glaucoma and optic neuropathy. Endogenous regeneration of retinal stem cells is the best alternative to retinal ganglion cells to replace retinal ganglion cell degenerative diseases. However, stem cell-based therapies rely on exogenous stem cell sources due to their limited availability. Among different types of stem cells, mesenchymal stem cells are highly transplantable because they have strong immunosuppressive properties and inhibit the release of pro-inflammatory cytokines, allowing autologous and allogeneic transplantation without the need for pharmacological immunosuppression.

In addition, MSCs can be transplanted directly without genetic modification or pretreatment, and can migrate to the site of tissue damage without forming teratomas after transplantation, and do not involve moral objections or moral disputes. Importantly, MSCs can be used directly for neuroprotection or to induce replacement therapy for nerve cells. These biological properties and the expansion potential of MSCs enable mesenchymal stem cells to treat different human diseases, particularly therapeutic applications of retinal ganglion cell degenerative diseases.