References:
1. Yoon KC, Im SK, Park YG, Jung YD, Yang SY, Choi J. Application of umbilical cord serum eyedrops for the treatment of dry eye syndrome. Cornea. 2006;25(2):268–272.
2. Yoon KC, You IC, Im SK, Jeong TS, Park YG, Choi J. Application of umbilical cord serum eyedrops for the treatment of neurotrophic keratitis. Ophthalmology. 2007;114(9):1637–1642.
3. Vajpayee RB, Mukerji N, Tandon R, Sharma N, Pandey RM, Biswas NR, Marhotra N, Melki SA. Evaluation of umbilical cord serum therapy for persistent corneal epithelial defects. Br J Ophthalmol. 2003;87(11):1312–1316
4. Karki P., Johnson J., Son D.-S., Aschner M., Lee E. Transcriptional Regulation of Human Transforming Growth Factor-α in Astrocytes. Molecular Neurobiology. 2017;54(2):964–976. doi: 10.1007/s12035-016-9705-9. [
5. Lambiase A., Aloe L., Centofanti M., et al. Experimental and clinical evidence of neuroprotection by nerve growth factor eye drops: implications for glaucoma. Proceedings of the National Acadamy of Sciences of the United States of America. 2009;106(32):13469–13474. doi: 10.1073/pnas.0906678106.
6. Chong R. S., Osborne A., Conceição R., Martin K. R. Platelet-derived growth factor preserves retinal synapses in a rat model of ocular hypertension. Investigative Ophthalmology & Visual Science. 2016;57(3):842–852. doi: 10.1167/iovs.15-1786
7. Giannaccare G1, Buzzi M, Fresina M, Velati C, Versura P. Efficacy of 2-Month Treatment With Cord Blood Serum Eye Drops in Ocular Surface Disease: An In Vivo Confocal Microscopy Study. Cornea. 2017 Aug;36(8):915-921.
8. Yoon KC, Heo H, Im SK, et al. Comparison of autologous serum and umbilical cord serum eye drops for dry eye syndrome. Am J Ophthalmol 2007;144:86–92.
9. Yoon KC Jeong IY Im SK Park YG Kim HJ Choi J . Therapeutic effect of umbilical cord serum eyedrops for the treatment of dry eye associated with graft-versus-host disease. Bone Marrow Transplant. 2007;39:231–235.
10. Sharma N, Goel M, Velpandian T, Titiyal JS, Tandon R, Vajpayee RB. Evaluation of umbilical cord serum therapy in acute ocular chemical burns. Invest Ophthalmol Vis Sci. 2011 Feb 25;52(2):1087-92.
11. Oh HJ, Jang JY, Li Z, Park SH, Yoon KC. Effects of umbilical cord serum eye drops in a mouse model of ocular chemical burn. Curr Eye Res. 2012 Dec;37(12):1084-90.
12. Yoon KC. Use of umbilical cord serum in ophthalmology.Chonnam Med J. 2014 Dec;50(3):82-5.
Efficacy of 2-Month Treatment With Cord Blood Serum Eye Drops in Ocular Surface Disease: An In Vivo Confocal Microscopy Study.
Abstract
PURPOSE:
To investigate the morphological changes of corneal epithelium and subbasal nerves by in vivo confocal microscopy in patients with ocular surface disease (OSD) treated with cord blood serum (CBS) eye drops.
METHODS:
Twenty patients with OSD (mean age 61.1 ± 12.6 years) were included in this prospective 1-arm study and treated with CBS eye drops for 2 months. Corneal sensitivity, Schirmer test score, breakup time, subjective symptoms [Ocular Surface Disease Index (OSDI) and Visual Analogue Scale (VAS)], and corneal staining were evaluated before (T0) and after (T1) treatment. In vivo confocal microscopy analyzed giant epithelial cells, subbasal nerve number and tortuosity, neuromas, beading, and dendritic cells (DCs) in the central cornea.
RESULTS:
OSDI, Visual Analogue Scale, and Oxford grading values significantly decreased at T1 versus T0 (respectively, 44.1 ± 18.9 vs. 74.2 ± 13.9; 3.7 ± 1.5 vs. 8.9 ± 0.9; and 2.4 ± 1.1 vs. 3.3 ± 1.3; P < 0.0001), whereas corneal sensitivity, Schirmer test score, and breakup time significantly increased (respectively, 49.5 ± 2.6 vs. 47.9 ± 2.9; 3.2 ± 2.0 vs. 2.4 ± 2.2; 4.6 ± 3.1 vs. 3.8 ± 2.1; P < 0.0001). Corneal nerve morphology improved at T1 versus T0 with a higher total nerve number (3.4 ± 1.6 vs. 2.5 ± 1.6 per frame) and lower tortuosity (3.0 ± 0.7 vs. 3.5 ± 0.6) (P < 0.01). The number of patients presenting with giant epithelial cells, beading, and neuromas decreased at T1. DC density did not change after treatment. The detection of neuromas and higher DC density at T0 were associated with greater OSDI reduction at T1 (P < 0.001).
CONCLUSIONS:
CBS eye drops significantly improved corneal nerve morphology and subjective symptoms in patients with severe OSD. The presence of neuromas and higher dendritic cell density at baseline were associated with greater reduction of discomfort symptoms after treatment.
Articles indicating safety and efficacy of treatment and or safety
Case Rep Ophthalmol Med. 2018; 2018: 2381296.
Published online 2018 Jul 25. doi: 10.1155/2018/2381296
PMCID: PMC6083596
PMID: 30147975
Topical Treatment with Cord Blood Serum in Glaucoma Patients: A Preliminary Report
Emilio Campos, 1 Piera Versura,
1 Giuseppe Giannaccare, 1 Adriana Terzi, 2 Silvia Bisti, 3 Stefano Di Marco, 3 andMarina Buzzi 2
1 Giuseppe Giannaccare, 1 Adriana Terzi, 2 Silvia Bisti, 3 Stefano Di Marco, 3 andMarina Buzzi 2
Abstract
Purpose
To report data which happened to be observed in two glaucoma patients treated with Cord Blood Serum (CBS) eye drops.
Design
A case report and retrospective data analysis.
Methods
CBS topical eye drops, characterized in advance for growth factors (GFs) content, were administered for two months with the aim to relieve their subjective symptoms, in two patients who had referred ocular surface discomfort, although in absence of any sign of keratopathy. As patients were also affected by advanced glaucoma at risk of vision loss and under treatment with hypotensive drugs, they had been also monitored over the same period with IOP controls and visual field tests in our unit.
Results
During subsequent visits, data from Mean Deviation and Pattern Standard Deviation in the visual fields were retrospectively collected and compared with before and after treatment with CBS, and an amelioration was observed.
Conclusions
Limbal Stem Cell Transplants:
Limbal stem cell transplantation: current perspectives. Marwan Raymond Atallah, Sotiria Palioura, Victor L Perez, and Guillermo Amescua. Clin Ophthalmol. 2016; 10: 593–602.
Abstract: Recently, various studies using adipose-derived stem cells (ADSCs) have been performed. However, the safety of ADSCs has not been determined, and protocols for isolating ADSCs have not been established. This study evaluated the activity and toxicity of residual collagenase in isolated ADSCs and the carcinogenicity of these cells. It evaluated the current use of ADSC-related procedures in South Korea as reference data for the authors’ studies. The study surveyed 100 private plastic surgical clinics, 68 plastic surgery departments at general and university hospitals, and 5 biotechnology companies by telephone. Among these, 14 institutions were surveyed using a more detailed questionnaire about ADSC-related procedures and methods of processing adipose tissue. The survey also evaluated the residual collagenase activity during five washes of the ADSC isolation procedure with furyl acryloyl-Leu-Gly-Pro-Ala (FALGPA) and ninhydrin assays. A 4-week toxicity study in non-obese diabetes/severe combined immunodeficiency (NOD/SCID) mice was performed as well as a tumorigenicity study in BALB/c-nu mice using ADSCs from the first and third washes. According to the findings, ADSC-related procedures were performed in 16 % of the private clinics and 14.7 % of the general hospitals surveyed. Among the 14 institutions, 0.1 % type 1
collagenase was used most frequently, and three washes generally were performed. After the first wash, residual collagenase activity was the same as in the blank group (saline only). No toxicity resulting from residual collagenase or tumorigenicity associated with the ADSCs was observed. The results of the current study may be beneficial for establishing safe ADSC isolation protocols and can be used as fundamental data for clinical applications involving ADSCs
Safety of Adipose Derived Stem Cells:
-
Aesthetic Plast Surg. 2013 Aug;37(4):802-8. doi: 10.1007/s00266-013-0156-7. Epub 2013 Jul. Safety of adipose derived stem cells and collagenase in fat preparation. Chang H, Do BR, Che JH, Kang BC, Kim JH, Kwon E, Kim JY, Min KH. Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, Seoul, Korea.
3. J Neuroophthalmol. 2009 Mar;29(1):43-9. A case of autoimmune-related retinopathy and optic neuropathy syndrome treated by autologous nonmyeloablative hematopoietic stem cell transplantation. Oyama Y, Burt RK, Thirkill C, Hanna E, Merrill K, Keltner J.
Autoimmune-related retinopathy and optic neuropathy (ARRON) syndrome is characterized by visual loss and often the presence of antibodies against retinal or optic nerve antigens in the absence of cancer. Limited success has been reported in treatment of ARRON syndrome with medications that suppress the immune system. In many patients, current strategies are insufficient to control the disease. A 47-year-old woman with progressive visual and hearing loss attributed to ARRON syndrome that was resistant to conventional therapies underwent autologous hematopoietic stem cell transplantation (HSCT). Clinical manifestations appeared to stabilize. This report suggests that autologous HSCT may have a therapeutic role in ARRON syndrome. PMID: 19458576 [PubMed – indexed for MEDLINE]
Exp Neurol. 2009 Apr;216(2):439-48
Umbilical cord blood mesenchymal stromal cells are neuroprotective and promote regeneration in a rat optic tract model.
Zwart I, Hill AJ, Al-Allaf F, Shah M, Girdlestone J, Sanusi AB, Mehmet H, Navarrete R, Navarrete C, Jen LS
Exploitation of the ability of stem cells to protect damaged neuronal tissue may be a more viable strategy than cell replacement for repair of the central nervous system (CNS). In this study we assessed the capacity of human umbilical cord blood (hUCB)-derived mesenchymal stromal cells (MSCs) to protect and promote regeneration of axotomized neurons within the rat optic system. The optic tract of neonatal rats was transected at the level of the lateral geniculate nucleus, and MSCs were introduced into the lesion site. MSCs survived well up to 2 weeks after grafting, and did not migrate significantly or differentiate. In the presence of MSC grafts, host axonal
processes were found to be present in the lesion site, and there was stimulation of an endogenous neural precursor population. Four weeks after grafting, retrograde tracer experiments demonstrated that grafted MSCs, as well as cells of a human fibroblast line, exerted a neuroprotective effect, rescuing a significant percentage of axotomized retinal ganglion cells (RGCs). Further experiments with retrograde and
anterograde tracers strongly indicated that MSCs could also promote regrowth of axotomized RGCs to their target, the superior colliculus (SC). Further analysis showed that hUCB-derived MSCs secreted several immunomodulatory and neurotrophic factors in vitro, including TGFbeta1, CNTF, NT-3 and BDNF, which are likely to play a role in neuroprotection. Our data indicate that hUCB-derived MSCs may be an easily accessible, widely available source of cells that can contribute towards neural repair through rescue and regeneration of injured neurons. PMID: 19320003 [PubMed – indexed for MEDLINE]
Graefes Arch Clin Exp Ophthalmol. 2009 Apr;247(4):503-14
Effects of bone-marrow mesenchymal stem cells transplanted into vitreous cavity of rat injured by ischemia/reperfusion.
Li N, Li XR, Yuan JQ
OBJECTIVE: To examine the survival, migration, integration, differentiation and the expression of various neurotrophic factors of bone-marrow mesenchymal stem cells (BMSCs) transplanted into the vitreous cavity of rats injured by ischemia/reperfusion(I/R). METHODS: The BMSCs were separated from rat marrow using the wall-sticking method, and cultured in vitro to expand. Flow cytometry detected the surface antigens of BMSCs. Ninety-six rats were randomly divided into four groups: normal control injected PBS(C+P), normal control injected BMSCs (C+B), ischemic/reperfusion injected PBS(I/R+P)and ischemic/reperfusion injected BMSCs(I/R+B). After retinal I/R injury was induced in each group by increasing intraocular pressure, 10 microl PBS and BMSC suspensions labeled by red fluorescence CM-Dil were immediately injected into the vitreous cavity. We observed the survival, migration and integration of BMSCs using confocal microscopy. The differentiation and expression of basic fibroblast growth factor
(bFGF), brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) of CM-Dil-labeled BMSCs were detected by immunofluorescent labeling and reserved by confocal microscopy. The expression of mRNA and proteins of bFGF, BDNF and CNTF were assayed by RT-PCR and Western Blot respectively. RESULTS: After transplantation to normal eyes, BMSCs labeled by CM-Dil were mostly present in the vitreous cavity, and did not migrate. After transplantation to I/R eyes, BMSCs labeled by CM-Dil were mostly present along with the inner limiting membrane. Only a few cells were integrated into the ganglion cell layer. Two or 4 weeks after transplantation, a few BMSCs labeled by CM-Dil were observed to express markers of neuron- neurone specific enolase (NSE), neurofilament (NF) and various neurotrophic factors. The BMSC-injected I/R model eyes showed less reduction in the number of RGCs than that of
the I/R eyes with PBS injection. CONCLUSIONS: BMSC transplantation is a valuable neuroprotection tool for the treatment of retina and optic nerve diseases.
Stem cells: a new paradigm for disease modeling and developing therapies for age-related macular degeneration.
Abstract: Age-related macular degeneration (AMD) is the leading cause of blindness in people over age 55 in the U.S. and the developed world. This condition leads to the progressive impairment of central visual acuity. There are significant limitations in the understanding of disease progression in AMD as well as a lack of effective methods of treatment. Lately, there has been considerable enthusiasm for application of stem cell biology for both disease modeling and therapeutic application. Human embryonic stem cells and induced pluripotent stem cells (iPSCs) have been used in cell culture assays and in vivo animal models. Recently a clinical trial was approved by FDA to investigate the safety and efficacy of the human embryonic stem cell- derived retinal pigment epithelium (RPE) transplantation in sub-retinal space of patients with dry AMD These studies suggest that stem cell research may provide both insight regarding disease development and progression, as well as direction for therapeutic innovation for the millions of patients afflicted with AMD.
Curr Opin Ophthalmol. 2012 May;23(3):226-34. doi: 10.1097/ICU.0b013e328352407d. Stem cell therapy for retinal disease
Wills Eye Institute Retina Service, Mid Atlantic Retina, Philadelphia, Pennsylvania 19107, USA. michael.tibbetts@gmail.com
Abstract: Stem cell therapy holds great promise for the treatment of retinal diseases. This review summarizes recent advances in stem cell biology, outlines ongoing clinical trials and details the obstacles that must be overcome for stem cell therapy to be a viable treatment for retinal disease. Stem cells can now be directed to specific retinal cell fates with high yields and acceptable purity
for clinical trials. New stemcell sources have been discovered including induced pluripotent stem
cells that can be derived from adult tissues then differentiated into multiple retinal cell types. The initial results of clinical trials of subretinal transplantation of human embryonic stem cell-derived retinal pigment epithelium cells in patients with Stargardt’s macular dystrophy and dry age-
related macular degeneration showed preliminary safety and possible visual acuity benefits. A phase I trial of intravitreally injected autologous bone marrow-derived mononuclear cells for hereditary retinal dystrophy demonstrated no evidence of toxicity with possible visual acuity benefits but no structural or functional changes. Ongoing trials are examining the trophic effects of undifferentiated umbilical cells for the treatment of geographic atrophy in age-related macular degeneration.
Stem cell therapy is a promising treatment under active investigation in multiple retinal diseases. Ongoing clinical trials should yield further insights into the potential for stem cell-based retinal therapies. PMID:22450217[PubMed – in process]
Stem cell based therapeutic applications in retinal degenerative diseases
Institute for Cellular Therapeutics, University of Louisville, 570 S. Preston Street, Suite 404, Louisville, KY 40202-1760, USA.
Abstract: Retinal degenerative diseases that target photoreceptors or the adjacent retinal pigment epithelium (RPE) affect millions of people worldwide. Retinal Degeneration (RD) is found in many different forms of retinal diseases including retinitis pigmentosa (RP), age-related macular degeneration (AMD), diabetic retinopathy, cataracts, and glaucoma. Effective treatment
for retinal degeneration has been widely investigated. Gene-replacement therapy has been shown to improve visual function in inherited retinal disease. However, this treatment was less effective with advanced disease. Stem cell-based therapy is being pursued as a potential alternative approach in the treatment of retinal degenerative diseases. In this review, we will focus
stem cell-based therapies in the pipeline and summarize progress in treatment of retinal degenerative disease. PMID:20859770[PubMed – indexed for MEDLINE.PMCID:PMC3408315
Stem Cell Res Ther. 2010 Jun 29;1(2):19.
Clinical and preclinical translation of cell based therapies using adipose tissue derived cells
Abstract: Adipose tissue is now recognized as an accessible, abundant, and reliable site for the isolation of adult stem cells suitable for tissue engineering and regenerative medicine applications. The past decade has witnessed an explosion of preclinical data relating to the isolation, characterization, cryopreservation, differentiation, and transplantation of freshly isolated stromal vascular fraction cells and adherent, culture-expanded, adipose-derived stromal/stem cells in vitro and in animal models. This body of work has provided evidence supporting clinical translational applications of adipose-derived cells in safety and efficacy trials. The present article reviews the case reports and phase I-III clinical evidence using autologous adipose-derived cells that have been published, to date, in the fields of gastroenterology, neurology, orthopedics, reconstructive surgery, and related clinical disciplines. Future directions and challenges facing the field are discussed and evaluated.
Full CBS references Feb 2019