|
1
|
Suleman A, Aluyi-Osa G, Ashipa F, Spadea L, Gagliano C, D’Esposito F, Zeppieri M, Musa M. Autologous blood in the management of ocular surface disorders. World J Exp Med 2024; 14:96412. [PMID: 39713083 PMCID: PMC11551708 DOI: 10.5493/wjem.v14.i4.96412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 09/23/2024] [Accepted: 10/22/2024] [Indexed: 10/31/2024] Open
Abstract
Autologous blood therapy has emerged as a promising modality in managing ocular surface disorders. This review provides a comprehensive overview of the current literature regarding the use of autologous blood in ocular surface disorders, encompassing its physiological basis, clinical applications, techniques, challenges, and future perspectives. The ocular surface, comprising the cornea, conjunctiva, and tear film, plays a critical role in maintaining visual function, and its disruption can lead to various pathological conditions. With its rich composition of growth factors, cytokines, and other bioactive molecules, autologous blood offers therapeutic potential in promoting corneal wound healing, reducing inflammation, and improving tear film stability. Clinical studies have demonstrated the efficacy and safety of autologous blood therapy in diverse ocular surface disorders, including persistent epithelial defects, neurotrophic keratopathy, and dry eye disease. However, challenges such as variability in treatment response, adverse effects, and optimal patient selection remain areas of concern. Further research is needed to elucidate the underlying mechanisms of action, refine treatment protocols, and explore synergistic approaches with other therapeutic modalities. Despite these challenges, autologous blood therapy holds promise as a valuable adjunctive treatment option for ocular surface disorders, offering new avenues for improving patient outcomes and quality of life. This review examines the mechanisms underlying ocular surface disorders while discussing existing autologous blood-based therapies for managing these disorders. Current clinical trials are also summarized, and a comparison between autologous blood therapy and conventional eyedrops is attempted. Finally, safe techniques and protocols for autologous blood medicine are elucidated, and adverse effects and future perspectives of this novel therapy are reviewed.
Collapse
Affiliation(s)
- Ayuba Suleman
- Department of Ophthalmology, Africa Eye Laser Centre, Km 7, Benin 300105, Nigeria
| | - Gladness Aluyi-Osa
- Department of Ophthalmology, Africa Eye Laser Centre, Km 7, Benin 300105, Nigeria
| | | | - Leopoldo Spadea
- Eye Clinic, Policlinico Umberto I, “Sapienza” University of Rome, Rome 00142, Italy
| | - Caterina Gagliano
- Department of Medicine and Surgery, University of Enna “Kore”, Enna 94100, Italy
- Mediterranean Foundation “G.B. Morgagni”, Catania 95125, Italy
| | - Fabiana D’Esposito
- Imperial College Ophthalmic Research Group Unit, Imperial College, London NW1 5QH, United Kingdom
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
| | - Mutali Musa
- Department of Optometry, University of Benin, Benin 3000283, Nigeria
| |
Collapse
|
|
2
|
Gagliano C, Foti R, Zeppieri M, Maniaci A, Lavalle S, Tancredi G, Gagliano G, Avitabile A, Cannizzaro L, Foti R. Umbilical Cord Blood Platelet Lysate Eyedrops for the Treatment of Severe Ocular Surface Disorders in Graft vs. Host Disease Patients: Clinical Study. Life (Basel) 2024; 14:1268. [PMID: 39459568 PMCID: PMC11509496 DOI: 10.3390/life14101268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 09/25/2024] [Accepted: 10/03/2024] [Indexed: 10/28/2024] Open
Abstract
Background: Graft-versus-host disease (GvHD) is an overactive systemic inflammatory response that can arise following allogeneic hematopoietic stem cell transplantation (HSCT). This condition occurs when the transplanted donor immune cells recognize the recipient's tissues as foreign and trigger an immune response against them. The ocular surface (eyelids, conjunctiva, meibomian glands, lacrimal glands, and cornea) is particularly involved in GvHD, and its response to existing treatments, including potent immunosuppressants and new targeted therapies, is undesirable, with such treatments often being ineffective. Human allogeneic umbilical cord blood platelet lysate stands out as a potent adjunct to conventional therapies for ocular surface disorders related to severe Dry Eye Disease. This study aimed to evaluate the safety and efficacy of umbilical cord blood platelet lysate eyedrops for the treatment of severe ocular surface disorders in graft-versus-host disease patients who have received previous unsuccessful treatments. Methods: This study was a prospective, non-comparative, interventional case series study involving 22 patients (10 females and 12 males) aged 25-46 years with severe ocular surface disorders that were unresponsive to standard treatments. The GvHD patients were categorized based on the severity of their ocular surface disorders into three groups: Group I: five patients with severe Dry Eye Disease and filamentary keratitis; Group II: eight patients suffering from severe blepharo-kerato-epitheliopathy; Group III: nine patients with corneal ulcers. Fresh umbilical cord blood (UCB) was obtained from healthy donors and subjected to centrifugation using a novel PRP preparation kit provided by Sciacca (AG) Cord blood bank, Italy in a one-step process. In all groups, the outcomes before and after treatment were evaluated by means of the OSDI (Ocular Surface Disease Index), SANDE (Symptom Assessment in Dry Eye) questionnaire, VAS (Visual Analogue Scale), slit lamp examination, Esthesiometry, Lissamine Green Staining, the NIBUT (Non-Invasive Break-Up Time) and BUT, fluorescein staining with digital photography and Oxford classification, the Schirmer Test, the Best Corrected Visual Acuity (BCVA), and Meibography. In Group III at each evaluation time, the size of the ulcer and its relative reduction compared to the baseline size were recorded. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, or pain, were also considered individually. Results: We observed a significant improvement in the SANDE, VAS, and OSDI scores; Schirmer Test; BUT; BCVA; and Oxford classification after treatment with allogeneic cord blood serum eyedrops. Nevertheless, pain and inflammation reduced markedly over time until complete healing in all cases. The mean reduction in the ulcer surface area (compared to baseline values) was significantly higher at all assessment points (p = 0.001 for day 7 and p < 0.001 for subsequent time points every 30 days for 90 days). At the last check-up (after 90 days of treatment), the number of ulcers (Group III, nine patients) with a reduction in size of greater than 50% was eight (88.8%), of which seven ulcers were completely healed. None of the patients experienced treatment-related local or systemic adverse events. In this study, using a relatively large number of cases, we demonstrated that the use of umbilical cord blood platelet lysate eyedrops is a safe, feasible, and effective curative approach for severe ocular surface disease in patients with GvHD. Conclusions: Our pilot study highlights the remarkable effectiveness of allogeneic cord blood serum eyedrops in patients with severe ocular surface disorders following GvHD who have shown an inadequate response to the usual treatments. It is mandatory to design future studies on the efficacy of this therapeutic approach for acute ocular, mucosal, and cutaneous GvHD.
Collapse
Affiliation(s)
- Caterina Gagliano
- Department of Medicine and Surgery, University of Enna “Kore”, Piazza dell’Università, 94100 Enna, Italy; (C.G.)
| | - Roberta Foti
- Division of Rheumatology, A.O.U. “Policlinico-San Marco”, 95123 Catania, Italy (R.F.)
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy
| | - Antonino Maniaci
- Department of Medicine and Surgery, University of Enna “Kore”, Piazza dell’Università, 94100 Enna, Italy; (C.G.)
| | - Salvatore Lavalle
- Department of Medicine and Surgery, University of Enna “Kore”, Piazza dell’Università, 94100 Enna, Italy; (C.G.)
| | | | | | | | | | - Rosario Foti
- Division of Rheumatology, A.O.U. “Policlinico-San Marco”, 95123 Catania, Italy (R.F.)
| |
Collapse
|
|
3
|
Lv X, Li H, Su S, Fan S. Advances in the ocular complications after hematopoietic stem cell transplantation. Ann Hematol 2024; 103:3867-3880. [PMID: 38403713 DOI: 10.1007/s00277-024-05678-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Accepted: 02/18/2024] [Indexed: 02/27/2024]
Abstract
Hematopoietic stem cell transplantation (HSCT) has benefited an increasing number of patients with hematological disease in the clinic. It is a curative therapy for malignant and nonmalignant hematological diseases. With the advancement and further clinical application of HSCT in recent years, the life expectancy of patients has increased, but complications have become more common. The occurrence of ocular complications is receiving increasing attention because they can seriously affect the quality of life of patients. Ocular complications require increased attention from clinicians because of their negative impact on patients and increasing incidence. Most of recent reports on posttransplant ocular complications involve ocular manifestations of graft-versus-host disease (GVHD), and a few ocular complications that do not originate from GVHD have also been reported. This review summarizes the diagnosis, scoring criteria, pathophysiology, and clinical manifestations of and common therapies for ocular graft-versus-host disease(oGVHD) after HSCT, and includes a description of some rare cases and novel therapies.
Collapse
Affiliation(s)
- Xiaoli Lv
- Department of Hematology, First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China
| | - Huibo Li
- Department of Hematology, First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China
| | - Sheng Su
- Eye Hospital, First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China.
| | - Shengjin Fan
- Department of Hematology, First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China.
- NHC Key Laboratory of Cell Transplantation, First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China.
| |
Collapse
|
|
4
|
Shahraki T, Baradaran-Rafii A, Ayyala R, Arabi A, Jarstad J, Memar F. New advances in medical management of dry eye: optimizing treatment strategies for enhanced relief. Int Ophthalmol 2024; 44:49. [PMID: 38337030 DOI: 10.1007/s10792-024-02978-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Accepted: 10/29/2023] [Indexed: 02/12/2024]
Abstract
PURPOSE Dry eye disease (DED) is a prevalent ocular surface disease that is conventionally characterized by tear film hyperosmolarity and instability. This review presents a summarized classification of DED, followed by a comprehensive discussion of the most recent topical and systemic medications and clinical recommendations for selecting the most appropriate option for each patient. METHODS An extensive literature search was conducted on electronic databases, such as PubMed, Scopus, and Web of Science, using keywords including "dry eye syndrome," "ocular surface disease," "medical management," "artificial tears," "topical immunomodulators," and "meibomian gland dysfunction." RESULTS The underlying reasons for DED can range from insufficient aqueous tear production to increased tear evaporation. Recent literature has provided a more in-depth understanding of the pathophysiology of DED by examining the tear film's lipid, aqueous, and mucin layers. However, despite these advancements, medical management of patients with symptomatic DED has not fully reflected this modernized knowledge of its pathophysiology. CONCLUSION To develop a rationalized strategy for treating DED, it is crucial to have updated knowledge of therapeutic options, their mechanisms of actions, and indications based on the DED type and underlying causes.
Collapse
Affiliation(s)
- Toktam Shahraki
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, No. 23, Paidarfard St., Boostan 9 St., Pasdaran Ave, Tehran, Iran.
| | - Alireza Baradaran-Rafii
- Department of Ophthalmology, University of South Florida, Morsani College of Medicine, Tampa, FL, USA
| | - Ramesh Ayyala
- Department of Ophthalmology, University of South Florida, Morsani College of Medicine, Tampa, FL, USA
| | - Amir Arabi
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, No. 23, Paidarfard St., Boostan 9 St., Pasdaran Ave, Tehran, Iran
| | - John Jarstad
- Department of Ophthalmology, University of South Florida, Morsani College of Medicine, Tampa, FL, USA
| | | |
Collapse
|
|
5
|
Kwaku Akowuah P, Junior Obinwanne C, Owusu E, Kyeremeh S, Bonsu K, Karikari LAA, Akyaa Akomeah F, Kyei Nkansah E, Kobia-Acquah E. Platelet-rich plasma for treating dry eye disease - A systematic review and meta-analysis. Cont Lens Anterior Eye 2024; 47:102091. [PMID: 37951738 DOI: 10.1016/j.clae.2023.102091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 10/20/2023] [Accepted: 11/04/2023] [Indexed: 11/14/2023]
Abstract
PURPOSE Dry eye disease has public health and economic significance. Platelet-rich plasma is rich in anti-inflammatory agents and growth factors, both beneficial for ocular surface repair. This study aimed to conduct a systematic review and meta-analysis to summarize the benefits of platelet-rich plasma for treating dry eye disease and its adverse effects. METHODS Prospective comparative studies using platelet-rich plasma as monotherapy for dry eye disease were included for efficacy assessment. Before-after studies were included for adverse events assessment. Data sources included PubMed, Google Scholar, Web of Science, and Scopus. A systematic review and meta-analysis protocol was pre-registered on PROSPERO (CRD42022347982). PRISMA guidelines were followed. The National Health Institute (NIH) quality assessment tool for before-after studies, the Cochrane risk of bias tool (RoB2), and the methodological index for non-randomized studies were used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. RESULTS 19 studies (10 comparative and 9 before-after) were included in the systematic review and meta-analysis. The occurrence rate of adverse effects was 2.6 % (95 % CI: 0.5 - 4.7). The pooled standardized mean difference (SMD) for dry eye symptoms was 0.81 (95 % CI: 0.25 - 1.37; I2 = 82 %; p < 0.00001; Z = 2.84, p = 0.004); tear quality was 0.44 (95 % CI: 0.06 - 0.81; I2 = 67 %; p = 0.003; Z = 2.26, p = 0.02); tear quantity was 0.45 (95 % CI: 0.03 - 0.88; I2 = 74 %; p = 0.0003; Z = 2.10, p = 0.04); and corneal staining 0.72 (95 % CI: 0.14 - 1.30; I2 = 85 %; p < 0.00001; Z = 2.43, p = 0.02). CONCLUSION The current study shows that platelet-rich plasma is efficacious in managing dry eye disease, significantly reducing dry eye signs and symptoms. Such significant improvements could translate to improved quality of life.
Collapse
Affiliation(s)
| | | | - Ebenezer Owusu
- College of Optometry, University of Houston, Houston, TX, USA.
| | - Sylvester Kyeremeh
- Department of Optometry and Visual Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Kwaku Bonsu
- College of Optometry, University of Houston, Houston, TX, USA.
| | | | - Felicia Akyaa Akomeah
- Department of Optometry and Visual Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Ernest Kyei Nkansah
- Centre for Eye Research Ireland, Environmental Sustainability and Health Institute, Technological University Dublin, Dublin, Ireland
| | - Emmanuel Kobia-Acquah
- Department of Optometry and Visual Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; Centre for Eye Research Ireland, Environmental Sustainability and Health Institute, Technological University Dublin, Dublin, Ireland.
| |
Collapse
|
|
6
|
Knab J, Rawson B, Harris D. Platelet Lysate. ESSENTIALS OF REGENERATIVE MEDICINE IN INTERVENTIONAL PAIN MANAGEMENT 2024:133-152. [DOI: 10.1007/978-3-031-50357-3_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
7
|
He Y, Wong H, Gu J, Lin L. Corneal Descemetocele Management with Multi-Layer Amniotic Membrane Transplantation in an Ocular Graft-versus-Host Disease Case. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1733. [PMID: 37893451 PMCID: PMC10607979 DOI: 10.3390/medicina59101733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 09/16/2023] [Accepted: 09/22/2023] [Indexed: 10/29/2023]
Abstract
Background: Chronic ocular graft-versus-host disease (oGVHD) is a common ocular complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by progressive inflammation of the ocular surface and refractory dry eye. In severe cases, sterile corneal perforation can occur, which poses a significant challenge, due to the low survival rate of grafts after corneal transplantation. Case Presentation: A 47-year-old female presented to our hospital with persistent dryness, foreign body sensation, and blurred vision in her left eye. Diagnosis of graft-versus-host disease with corneal descemetocele in the left eye was made after detailed history review and thorough examination. Multi-layer amniotic membrane transplantation was performed in the affected eye, resulting in amelioration of the patient's symptoms. This amelioration of symptoms provided the patient with a level of comfort that permitted additional time while awaiting corneal transplantation. Conclusions: We report a successful case of multi-layer amniotic membrane transplantation for the management of corneal descemetocele following allo-HSCT.
Collapse
Affiliation(s)
- Yunjiao He
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Sun Yat-sen University, Guangzhou 510060, China; (Y.H.); (H.W.); (J.G.)
- Department of Laboratory, Dehong People’s Hospital, Dehong 678400, China
| | - Hiufong Wong
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Sun Yat-sen University, Guangzhou 510060, China; (Y.H.); (H.W.); (J.G.)
| | - Jianjun Gu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Sun Yat-sen University, Guangzhou 510060, China; (Y.H.); (H.W.); (J.G.)
| | - Lixia Lin
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Sun Yat-sen University, Guangzhou 510060, China; (Y.H.); (H.W.); (J.G.)
| |
Collapse
|
|
8
|
Tian Y, Zhang T, Li J, Tao Y. Advances in development of exosomes for ophthalmic therapeutics. Adv Drug Deliv Rev 2023; 199:114899. [PMID: 37236425 DOI: 10.1016/j.addr.2023.114899] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 04/18/2023] [Accepted: 05/21/2023] [Indexed: 05/28/2023]
Abstract
Exosomes contain multiple bioactive molecules and maintain the connection between cells. Recent advances in exosome-based therapeutics have witnessed unprecedented opportunities in treating ophthalmic diseases, including traumatic diseases, autoimmune diseases, chorioretinal diseases and others. Utilization of exosomes as delivery vectors to encapsulate both drugs and therapeutic genes could yield higher efficacy and avoid the unnecessary immune responses. However, exosome-based therapies also come with some potential ocular risks. In this review, we first present a general introduction to exosomes. Then we provide an overview of available applications and discuss their potential risks. Moreover, we review recently reported exosomes as delivery vectors for ophthalmic diseases. Finally, we put forward future perspectives to grapple with its translation and underlying issues.
Collapse
Affiliation(s)
- Ying Tian
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China
| | - Tao Zhang
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China
| | - Jing Li
- Beijing Key Laboratory of DNA Damage Response, College of Life Sciences, Capital Normal University, Beijing 100048, PR China
| | - Yong Tao
- Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China.
| |
Collapse
|
|
9
|
Chiang TL, Sun YC, Wu JH, Hsieh YT, Huang WL, Chen WL. The ocular graft-versus-host disease: the path from current knowledge to future managements. Eye (Lond) 2023; 37:1982-1992. [PMID: 36333534 PMCID: PMC10333261 DOI: 10.1038/s41433-022-02288-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 08/26/2022] [Accepted: 10/07/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Graft-versus-host disease (GVHD) is one of the major complications of allogenic haematopoietic stem cell transplantation (HSCT). The manifestation of ocular GVHD (oGVHD) is variable and may involve cornea, lacrimal gland, conjunctiva, eyelid, and/or nasolacrimal duct. We reviewed and summarized the current managements of oGVHD with specific focus on the emerging therapeutic advances. METHODS PubMed, Web of Science, and Google Scholar were searched for relevant literatures published within 20 years. Keywords used included "Graft-Versus-Host Disease", "GVHD", "ocular", "ocular surface", "ocular GVHD", "oGVHD", "dry eye", "keratitis", etc. RESULTS: Current managements of oGVHD can be classified into topical immunosuppressants, local tear-preservatory treatments, local non-pharmacological/surgical interventions, and systemic treatments. Additionally, some innovative therapies with promising treatment effects have been proposed, including topical target therapies, epitheliotrophic and neurotrophic treatments, recombinant DNase eye drops, mesenchymal stromal cell injection, and more. CONCLUSIONS Clinical managements of oGVHD are administered in a symptom-based, stepwise manner. The advances in innovative therapies may help improve clinical outcomes, and it is essential that physicians stay updated with these novel treatment options.
Collapse
Affiliation(s)
- Tung-Lin Chiang
- School of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yi-Chen Sun
- Department of Ophthalmology, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan
- College of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Jo-Hsuan Wu
- Shiley Eye Institute and Viterbi Family Department of Ophthalmology, University of California, San Diego, La Jolla, CA, USA
| | - Ying-Tung Hsieh
- School of Medicine, National Taiwan University, Taipei, Taiwan
| | - Wei-Lun Huang
- Department of Ophthalmology, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Wei-Li Chen
- Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.
- Advanced Ocular Surface and Corneal Nerve Regeneration Centre, National Taiwan University Hospital, Taipei, Taiwan.
- Department of Ophthalmology, College of Medicine, National Taiwan University, Taipei, Taiwan.
| |
Collapse
|
|
10
|
Lozano M, Cid J. How do we forecast tomorrows' transfusion: Non-transfusional hemotherapy. Transfus Clin Biol 2023; 30:282-286. [PMID: 36754141 DOI: 10.1016/j.tracli.2023.01.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Accepted: 01/31/2023] [Indexed: 02/09/2023]
Abstract
Hemotherapy is the treatment of diseases by the use of blood or blood products from blood donation (by others of for oneself). It is clear that blood components transfusion represents the most important part of the activities of the professionals (doctors, nurses, technicians…) working in hemotherapy. But there are others forms of hemotherapy that are steadily growing, that we will discuss: plasma exchange, mononuclear cells collections for cellular therapies, extracorporeal photoapheresis, ABO antigen specific immunoadsorption and autologous platelet lysate.
Collapse
Affiliation(s)
- Miquel Lozano
- Apheresis and Cellular Therapy Unit. Department of Hemotherapy and Hemostasis, Clinic Institute of Hematology and Oncology, Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona, Barcelona. Spain.
| | - Joan Cid
- Apheresis and Cellular Therapy Unit. Department of Hemotherapy and Hemostasis, Clinic Institute of Hematology and Oncology, Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona, Barcelona. Spain
| |
Collapse
|
|
11
|
Tappeiner C, Heiligenhaus A, Halter JP, Miserocchi E, Bandello F, Goldblum D. Challenges and concepts in the diagnosis and management of ocular graft-versus-host disease. Front Med (Lausanne) 2023; 10:1133381. [PMID: 36891189 PMCID: PMC9987249 DOI: 10.3389/fmed.2023.1133381] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 01/18/2023] [Indexed: 02/19/2023] Open
Abstract
Graft-versus-host disease (GVHD) is characterized by tissue inflammation in the host following an allogeneic hematopoietic cell transplantation (HCT). The pathophysiology is complex and only incompletely understood yet. Donor lymphocyte interaction with the histocompatibility antigens of the host plays a crucial role in the pathogenesis of the disease. Inflammation may affect multiple organs and tissues, e.g., the gastrointestinal tract, liver, lung, fasciae, vaginal mucosa, and the eye. Subsequently, alloreactive donor-derived T and B lymphocytes may lead to severe inflammation of the ocular surface (i.e., cornea and conjunctiva) and the eyelids. Furthermore, fibrosis of the lacrimal gland may lead to severe dry eye. This review focuses on ocular GVHD (oGVHD) and provides an overview of current challenges and concepts in the diagnosis and management of oGVHD. Ophthalmic manifestations, diagnostic procedures, grading of severity and recommendations for ophthalmic examination intervals are provided. Management of ocular surface disease with lubricants, autologous serum eye drops, topical anti-inflammatory agents and systemic treatment options are described based on the current evidence. Ocular surface scarring and corneal perforation are severe complications of oGVHD. Therefore, ophthalmic screening and interdisciplinary treatment approaches are highly relevant to improve the quality of life of patients and to prevent potentially irreversible visual loss.
Collapse
Affiliation(s)
- Christoph Tappeiner
- Department of Ophthalmology, Pallas Klinik, Olten, Switzerland.,Department of Ophthalmology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.,Department of Ophthalmology, San Raffaele Scientific Institute, University Vita-Salute, Milan, Italy.,Faculty of Medicine, University of Bern, Bern, Switzerland
| | - Arnd Heiligenhaus
- Department of Ophthalmology at St. Franziskus Hospital, Muenster, Germany
| | - Joerg P Halter
- Department of Hematology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Elisabetta Miserocchi
- Department of Ophthalmology, San Raffaele Scientific Institute, University Vita-Salute, Milan, Italy
| | - Francesco Bandello
- Department of Ophthalmology, San Raffaele Scientific Institute, University Vita-Salute, Milan, Italy
| | - David Goldblum
- Department of Ophthalmology, Pallas Klinik, Olten, Switzerland.,Faculty of Medicine, University of Basel, Basel, Switzerland
| |
Collapse
|
|
12
|
Sugar A, Hussain M, Chamberlain W, Dana R, Kelly DP, Ta C, Irvine J, Daluvoy M, Perez V, Olson J, Jhanji V, Walts TA, Stulting RD, Waller EK, Jagirdar N. A Randomized Trial of Topical Fibrinogen-Depleted Human Platelet Lysate Treatment of Dry Eye Secondary to Chronic Graft-versus-Host Disease. OPHTHALMOLOGY SCIENCE 2022; 2:100176. [PMID: 36245754 PMCID: PMC9562362 DOI: 10.1016/j.xops.2022.100176] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 05/25/2022] [Accepted: 05/26/2022] [Indexed: 11/29/2022]
Abstract
Purpose The purpose of the study was to evaluate, as a pilot trial, safety and tolerability of CAM-101 10% and 30% topical ophthalmic fibrinogen-depleted human platelet lysate (FD hPL) solution in patients with dry eye disease (DED) secondary to graft-versus-host disease (GvHD) after 6 weeks of treatment. Design A phase I/II, pilot, prospective, multicenter, randomized, double-masked clinical trial. Participants Patients with DED secondary to GvHD. Methods Sixty-four adult patients were stratified by "symptom severity" (Ocular Surface Disease Index [OSDI], ocular discomfort Visual Analog Scale (VAS), ocular symptom frequency, and use of artificial tears) and then randomized 1:1:1 to CAM-101 (FD hPL) at 10% or 30% concentration or an electrolyte (Plasma-Lyte A) vehicle control, 1 drop in both eyes, 4 times daily, for 42 days. After 42 days, control patients were offered 42 days of open-label treatment with 30% FD hPL. Main Outcome Measures Primary outcome safety measures were ocular and systemic adverse events and the number of patients in each group with clinically significant change from normal to abnormal in any ocular findings. Secondary outcomes were changes from baseline to day 42 in ocular discomfort, OSDI, fluorescein corneal staining, and lissamine green conjunctival staining relative to the vehicle control. The ocular symptom frequency was assessed on a 100-point VAS. Results FD hPL 10% and 30% were safe and well tolerated. Relative to the vehicle control, significant decreases from baseline to day 42 were seen in the FD hPL 30% group with regard to ocular discomfort (mean decrease = -18.04; P = 0.018), frequency of burning/stinging (-20.23; P = 0.022), eye discomfort (-32.97; P < 0.001), eye dryness (-21.61; P = 0.020), pain (-15.12; P = 0.044), photophobia (-24.33; P = 0.0125), and grittiness (-20.08; P = 0.0185). Decreases were also seen for itching and foreign body sensation, though not statistically significant. Improvements were seen in tear breakup time (mean increase = 1.30 seconds; P = 0.082) and the investigator's global evaluation 4-point scale (mean decrease = -0.86; P = 0.026). Corneal fluorescein staining was not improved. The OSDI had a mean decrease of -8.88 compared to the vehicle, although not statistically significant. Conclusions Fibrinogen-depleted human platelet lysate appears to be well tolerated, with no significant toxicity at concentrations of 10% and 30%. These initial data suggest some efficacy, especially for subjective outcome measures relative to baseline assessments and treatment with the vehicle, but larger studies are needed to confirm these effects.
Collapse
Key Words
- AE, adverse event
- ASTs, autologous serum tears
- CI, confidence interval
- DED, dry eye disease
- Dry eye disease
- FD hPL, fibrinogen-depleted human platelet lysate
- Graft versus host disease
- GvHD, graft-versus-host disease
- HSCT, hematopoietic stem cell transplant
- Human platelet
- OSDI, ocular surface disease index
- Ocular surface
- PRP, platelet-rich plasma
- SAE, severe adverse event
- Serum tears
- VAS, Visual Analog Scale
Collapse
Affiliation(s)
- Alan Sugar
- WK Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan
| | - Munira Hussain
- WK Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan
| | - Winston Chamberlain
- Casey Eye Institute, and Department of Ophthalmology, Oregon Health and Science University, Portland, Oregon
| | - Reza Dana
- Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
| | | | - Christopher Ta
- Department of Ophthalmology, School of Medicine, Stanford University, Stanford, California
| | - John Irvine
- Doheny Eye Center, UCLA, Los Angeles, California
| | | | - Victor Perez
- Duke University Eye Center, Durham, North Carolina
| | - Joshua Olson
- Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota
| | - Vishal Jhanji
- UPMC Eye Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | | | - Robert Doyle Stulting
- Cambium Medical Technologies LLC, Atlanta, Georgia
- Woolfson Eye Institute, Atlanta, Georgia
| | - Edmund K. Waller
- Cambium Medical Technologies LLC, Atlanta, Georgia
- Winship Cancer Institute of Emory University, Atlanta, Georgia
| | | |
Collapse
|
|
13
|
Deng X, Gould M, Ali MA. A review of current advancements for wound healing: Biomaterial applications and medical devices. J Biomed Mater Res B Appl Biomater 2022; 110:2542-2573. [PMID: 35579269 PMCID: PMC9544096 DOI: 10.1002/jbm.b.35086] [Citation(s) in RCA: 77] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 04/28/2022] [Accepted: 04/30/2022] [Indexed: 12/12/2022]
Abstract
Wound healing is a complex process that is critical in restoring the skin's barrier function. This process can be interrupted by numerous diseases resulting in chronic wounds that represent a major medical burden. Such wounds fail to follow the stages of healing and are often complicated by a pro‐inflammatory milieu attributed to increased proteinases, hypoxia, and bacterial accumulation. The comprehensive treatment of chronic wounds is still regarded as a significant unmet medical need due to the complex symptoms caused by the metabolic disorder of the wound microenvironment. As a result, several advanced medical devices, such as wound dressings, wearable wound monitors, negative pressure wound therapy devices, and surgical sutures, have been developed to correct the chronic wound environment and achieve skin tissue regeneration. Most medical devices encompass a wide range of products containing natural (e.g., chitosan, keratin, casein, collagen, hyaluronic acid, alginate, and silk fibroin) and synthetic (e.g., polyvinyl alcohol, polyethylene glycol, poly[lactic‐co‐glycolic acid], polycaprolactone, polylactic acid) polymers, as well as bioactive molecules (e.g., chemical drugs, silver, growth factors, stem cells, and plant compounds). This review addresses these medical devices with a focus on biomaterials and applications, aiming to deliver a critical theoretical reference for further research on chronic wound healing.
Collapse
Affiliation(s)
- Xiaoxuan Deng
- Centre for Bioengineering & Nanomedicine (Dunedin), Department of Oral Rehabilitation, Faculty of Dentistry, University of Otago, Dunedin, New Zealand
| | - Maree Gould
- Centre for Bioengineering & Nanomedicine (Dunedin), Department of Oral Rehabilitation, Faculty of Dentistry, University of Otago, Dunedin, New Zealand
| | - M Azam Ali
- Centre for Bioengineering & Nanomedicine (Dunedin), Department of Oral Rehabilitation, Faculty of Dentistry, University of Otago, Dunedin, New Zealand
| |
Collapse
|
|
14
|
Platelet Lysate as a Promising Medium for Nanocarriers in the Management and Treatment of Ocular Diseases. CURRENT OPHTHALMOLOGY REPORTS 2022. [DOI: 10.1007/s40135-022-00285-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
|
|
15
|
Holtzman NG, Pavletic SZ. The clinical landscape of chronic graft-versus-host disease management in 2021. Br J Haematol 2021; 196:830-848. [PMID: 34599519 DOI: 10.1111/bjh.17835] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 08/27/2021] [Accepted: 09/02/2021] [Indexed: 12/16/2022]
Abstract
Chronic graft-versus-host disease (cGVHD) is an important systemic complication of allogeneic haematopoietic stem cell transplantation with heterogeneous, multi-organ involvement that can lead to increased morbidity and mortality. Despite significant advances in understanding the complex pathophysiology driving the disease, curative treatment options remain suboptimal. The past decade, however, has seen much growth in collaborative research efforts and standardization of criteria for clinical trials that have led to discovery of several new second-line therapies in cGVHD. The key to successful cGVHD control and management includes a comprehensive and sustained multidisciplinary effort with emphasis on ancillary and supportive care for these patients. The focus of this review is to summarize the new developments in systemic, organ-specific, and topical treatments in the management of cGVHD that emerged since the 2014 NIH consensus conference.
Collapse
Affiliation(s)
- Noa G Holtzman
- Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Steven Z Pavletic
- Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| |
Collapse
|
|
16
|
A purified human platelet pellet lysate rich in neurotrophic factors and antioxidants repairs and protects corneal endothelial cells from oxidative stress. Biomed Pharmacother 2021; 142:112046. [PMID: 34426259 DOI: 10.1016/j.biopha.2021.112046] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/09/2021] [Accepted: 08/12/2021] [Indexed: 12/13/2022] Open
Abstract
Human platelet lysate (HPL) is a complex mixture of potent bioactive molecules instrumental in tissue repair and regeneration. Due to their remarkable safety, cost-effective production, and availability at global level from collected platelet concentrates, HPLs can become a powerful biotherapy for various therapeutic applications, if standardized and carefully validated through pre-clinical and clinical studies. In this work, the possibility to use a tailor-made HPL as a corneal transplant alternative to treat the gradual decrease in the number of corneal endothelial cells (CECs) associated with aging, was evaluated. The HPL preparation was thoroughly characterized using various proteomics tools that revealed a remarkable richness in multiple growth factors and antioxidants. Treatment of B4G12 and BCE C/D-1b CECs with the HPL increased their viability, enhanced the wound closure rate, and maintained cell growth and typical hexagonal morphology. Besides, this HPL significantly protected against tert-butyl hydroperoxide (TBHP)-induced oxidative stress as evidenced by increasing CEC viability, decreased cell death and reactive oxygen species formation, and enhanced antioxidant capacity. Proteomics analysis of treated CECs confirmed that HPL treatment triggered the corneal healing pathway and enhanced oxidative stress. These data strongly support further pre-clinical evaluation of this tailor-made HPL as a novel CEC regeneration biotherapy. HPL treatment may eventually represent a pragmatic and cost-effective alternative to corneal transplant to treat damages of the corneal endothelium which is a major cause of blindness worldwide.
Collapse
|
|
17
|
Ogawa Y, Kawakami Y, Tsubota K. Cascade of Inflammatory, Fibrotic Processes, and Stress-Induced Senescence in Chronic GVHD-Related Dry Eye Disease. Int J Mol Sci 2021; 22:ijms22116114. [PMID: 34204098 PMCID: PMC8201206 DOI: 10.3390/ijms22116114] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/30/2021] [Accepted: 05/31/2021] [Indexed: 01/12/2023] Open
Abstract
Ocular graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation. Ocular GVHD affects recipients' visual function and quality of life. Recent advanced research in this area has gradually attracted attention from a wide range of physicians and ophthalmologists. This review highlights the mechanism of immune processes and the molecular mechanism, including several inflammation cascades, pathogenic fibrosis, and stress-induced senescence related to ocular GVHD, in basic spectrum topics in this area. How the disease develops and what kinds of cells participate in ocular GVHD are discussed. Although the classical immune process is a main pathological pathway in this disease, senescence-associated changes in immune cells and stem cells may also drive this disease. The DNA damage response, p16/p21, and the expression of markers associated with the senescence-associated secretory phenotype (SASP) are seen in ocular tissue in GVHD. Macrophages, T cells, and mesenchymal cells from donors or recipients that increasingly infiltrate the ocular surface serve as the source of increased secretion of IL-6, which is a major SASP driver. Agents capable of reversing the changes, including senolytic reagents or those that can suppress the SASP seen in GVHD, provide new potential targets for the treatment of GVHD. Creating innovative therapies for ocular GVHD is necessary to treat this intractable ocular disease.
Collapse
Affiliation(s)
- Yoko Ogawa
- Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan;
- Correspondence: ; Tel.: +81-3-3353-1211
| | - Yutaka Kawakami
- Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan;
- Department of Immunology, School of Medicine, International University of Health and Welfare, Chiba 286-8686, Japan
| | - Kazuo Tsubota
- Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan;
| |
Collapse
|
|
18
|
Nair S, Vanathi M, Mukhija R, Tandon R, Jain S, Ogawa Y. Update on ocular graft-versus-host disease. Indian J Ophthalmol 2021; 69:1038-1050. [PMID: 33913829 PMCID: PMC8186644 DOI: 10.4103/ijo.ijo_2016_20] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Ocular graft-versus-host disease (oGVHD) occurs as a complication following hematopoietic stem cell transplantation and is associated with significant ocular morbidity resulting in a marked reduction in the quality of life. With no current consensus on treatment protocols, management becomes challenging as recurrent oGVHD often refractory to conventional treatment. Most authors now diagnose and grade the disease based on criteria provided by the National Institutes of Health Consensus Conference (NIH CC) or the International Chronic oGVHD (ICCGVHD) consensus group. This article will provide an insight into the diagnostic criteria of oGVHD, its classification, and clinical severity grading scales. The inflammatory process in oGVHD can involve the entire ocular surface including the eyelids, meibomian gland, corneal, conjunctiva, and lacrimal system. The varied clinical presentations and treatment strategies employed to manage them have been discussed in the present study. The recent advances in ocular surface imaging in oGVHD patients such as the use of meibography and in vivo confocal microscopy may help in early diagnosis and prognostication of the disease. Researching tear proteomics and identification of novel potential tear biomarkers in oGVHD patients is an exciting field as they may help in objectively diagnosing the disease and monitoring the response to treatment.
Collapse
Affiliation(s)
- Sridevi Nair
- Cornea, Cataract & Refractive Surgery Services, Dr R P Centre, All India Institute of Medical Sciences, New Delhi, India
| | - Murugesan Vanathi
- Cornea, Cataract & Refractive Surgery Services, Dr R P Centre, All India Institute of Medical Sciences, New Delhi, India
| | - Ritika Mukhija
- Cornea, Cataract & Refractive Surgery Services, Dr R P Centre, All India Institute of Medical Sciences, New Delhi, India
| | - Radhika Tandon
- Cornea, Cataract & Refractive Surgery Services, Dr R P Centre, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Jain
- Department of Ophthalmology, University of Chicago, USA
| | - Yoko Ogawa
- Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan
| |
Collapse
|
|
19
|
Bruscolini A, Gharbiya M, Sacchetti M, Plateroti R, Ralli M, Moramarco A, Greco A, Lambiase A. Involvement of ocular surface in graft-versus-host disease: An update from immunopathogenesis to treatment. J Cell Physiol 2021; 236:6190-6199. [PMID: 33507561 DOI: 10.1002/jcp.30304] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 01/13/2021] [Accepted: 01/19/2021] [Indexed: 01/14/2023]
Abstract
Graft-versus-host disease is a common complication of hematopoietic stem cell transplantation and the ocular surface is a main target of inflammatory reaction.
Collapse
Affiliation(s)
- Alice Bruscolini
- Department of Sense Organs, Sapienza University of Rome, Rome, Italy
| | - Magda Gharbiya
- Department of Sense Organs, Sapienza University of Rome, Rome, Italy
| | - Marta Sacchetti
- Department of Sense Organs, Sapienza University of Rome, Rome, Italy
| | - Rocco Plateroti
- Department of Sense Organs, Sapienza University of Rome, Rome, Italy
| | - Massimo Ralli
- Department of Sense Organs, Sapienza University of Rome, Rome, Italy
| | | | - Antonio Greco
- Department of Sense Organs, Sapienza University of Rome, Rome, Italy
| | | |
Collapse
|
|
20
|
You J, Hodge C, Hoque M, Petsoglou C, Sutton G. Human Platelets and Derived Products in Treating Ocular Surface Diseases - A Systematic Review. Clin Ophthalmol 2020; 14:3195-3210. [PMID: 33116370 PMCID: PMC7567560 DOI: 10.2147/opth.s265701] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 08/26/2020] [Indexed: 12/26/2022] Open
Abstract
Human platelet products have emerged as an alternative treatment for a range of ocular surface diseases such as dry eye and corneal ulceration. With significant therapeutic potential and increasing popularity, this study aimed to conduct a systematic review to detail the various production methods involved in generating platelet-derived products, compare and analyze clinical findings across available studies, and disseminate the relative advantages, limitations, and challenges of using platelet products to treat ocular surface disease. Thirty-eight clinical studies were identified, excluding studies conducted in animals and non-English language. Studies reported clinical outcomes, which included ocular surface disease index, best-corrected visual acuity, and corneal fluorescein staining. Most clinical studies reported improved patient signs and symptoms with an increasing variety of human platelet products including platelet rich plasma eye drops, human platelet lysate and platelet gels. However, due to variations in production methods, and study designs as well as confusing terminology, it was suggested that characterization of platelet products is needed for proper evaluation across studies.
Collapse
Affiliation(s)
- Jingjing You
- Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.,School of Optometry and Vision Science, UNSW Sydney, Sydney, NSW, Australia
| | - Chris Hodge
- Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.,Vision Eye Institute, Chatswood, Sydney, NSW, Australia.,NSW Tissue Bank, Sydney, NSW, Australia.,Graduate School of Health, University of Technology Sydney, Sydney, NSW, Australia
| | | | - Constantinos Petsoglou
- Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.,NSW Tissue Bank, Sydney, NSW, Australia
| | - Gerard Sutton
- Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.,Vision Eye Institute, Chatswood, Sydney, NSW, Australia.,NSW Tissue Bank, Sydney, NSW, Australia
| |
Collapse
|
|
21
|
Recent developments in regenerative ophthalmology. SCIENCE CHINA-LIFE SCIENCES 2020; 63:1450-1490. [PMID: 32621058 DOI: 10.1007/s11427-019-1684-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 03/21/2020] [Indexed: 12/13/2022]
Abstract
Regenerative medicine (RM) is one of the most promising disciplines for advancements in modern medicine, and regenerative ophthalmology (RO) is one of the most active fields of regenerative medicine. This review aims to provide an overview of regenerative ophthalmology, including the range of tools and materials being used, and to describe its application in ophthalmologic subspecialties, with the exception of surgical implantation of artificial tissues or organs (e.g., contact lens, artificial cornea, intraocular lens, artificial retina, and bionic eyes) due to space limitations. In addition, current challenges and limitations of regenerative ophthalmology are discussed and future directions are highlighted.
Collapse
|
|
22
|
Liu J, Wang W, Wang X, Yu D, Wang Z, Wang W. PL/Vancomycin/Nano-hydroxyapatite Sustained-release Material to Treat Infectious Bone Defect. Open Life Sci 2020. [DOI: 10.1515/biol-2020-0011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
AbstractObjectiveTo evaluate the therapeutic effect of platelet lysate (PL)/vancomycin/nano-hydroxyapatite sustained-release material on treating staphylococcus aureus-induced infectious bone defects.Methods40 New Zealand white rabbits were inoculated with staphylococcus aureus to construct the chronic tibial infectious bone defect model. After incision, debridement and washing, control group 1 was not given any filling, control group 2 was filled with PL/nano-hydroxyapatite sustained release material, control group 3 was filled with vancomycin/ nano-hydroxyapatite sustained release material, and the treatment group was filled with PL/vancomycin/nano-hydroxyapatite sustained-release material. Afterwards, the drug release profiles were determined in vitro and in vivo. Then, X-rays and bone specimens were used to evaluate the efficacy of the treatments.ResultsTGF-β and PDGF were effectively released for 28 days in vitro. In addition, results of the inhibition zone experiment of the composite material proved that vancomycin had favorable antibacterial activity, which effectively suppressed bacteria for as long as 43 days, thus achieving the sustained-release antibacterial effect. The drug release profiles in vitro also demonstrated that the vancomycin concentration within the lesion region was the highest in composite material, and the infection in experimental rabbits was markedly alleviated. The original backbone deformity regained the normal shape, the normal bone marrow structure began to recover 6 weeks later, and the nano-hydroxyapatite transformed into the trabecula structure. By contrast, the inflammation in the control group still existed, with no obvious new bone formation.ConclusionThe PL/vancomycin/nano-hydroxyapatite sustained-release material effectively treats chronic infectious bone defects.
Collapse
Affiliation(s)
- Jianhui Liu
- Department of Orthopaedics,First Affiliated Hospital of Harbin Medical University,Harbin Heilongjiang,China
- Department of orthopedics, the 962st Hospital of PLA,Harbin Heilongjiang,China
| | - Wantao Wang
- Department of Orthopaedics,First Affiliated Hospital of Harbin Medical University,Harbin Heilongjiang,China
| | - Xinpeng Wang
- Department of orthopedics, the 962st Hospital of PLA,Harbin Heilongjiang,China
| | - Damiao Yu
- Department of Orthopaedics,First Affiliated Hospital of Harbin Medical University,Harbin Heilongjiang,China
| | - Zhenglei Wang
- Department of orthopedics, the 962st Hospital of PLA,Harbin Heilongjiang,China
| | - Wenbo Wang
- Department of Orthopaedics,First Affiliated Hospital of Harbin Medical University,Harbin Heilongjiang,China
| |
Collapse
|
|
23
|
Bonferoni MC, Rossi S, Sandri G, Caramella C, Del Fante C, Perotti C, Miele D, Vigani B, Ferrari F. Bioactive Medications for the Delivery of Platelet Derivatives to Skin Wounds. Curr Drug Deliv 2019; 16:472-483. [PMID: 30894109 PMCID: PMC6637103 DOI: 10.2174/1381612825666190320154406] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 02/24/2019] [Accepted: 03/13/2019] [Indexed: 12/13/2022]
Abstract
Chronic wounds are the result of alterations in the complex series of events of physiological wound healing. In particular, the prolonged inflammation results in increased protease activity, in the deg-radation of extracellular matrix (ECM) and of growth factors (GFs). The relevance of platelet GFs in maintaining and restoring the complex equilibrium of different moments in wound healing is well recog-nized. Moreover, the observed decrease of their levels in chronic wounds suggested a possible therapeutic role of the external application to the wounds. It has been also pointed out that tissue regeneration can be more efficiently obtained by the synergic use of different GFs. Platelet derivatives such as platelet-rich plasma (PRP) and platelet lysate (PL) are able to release GFs in a balanced pool. Their therapeutic use in regenerative medicine and wound healing has been therefore more and more frequently proposed in clini-cal trials and in the literature. The development of a suitable formulation able to control the GFs release rate, to protect the GFs, and to assure their prolonged contact with the wound site, is of paramount im-portance for the therapeutic success. The present review considers some formulation approaches for PRP and PL application to wounds
Collapse
Affiliation(s)
| | - Silvia Rossi
- Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy
| | - Giuseppina Sandri
- Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy
| | - Carla Caramella
- Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy
| | - Claudia Del Fante
- Immunohaematology and Transfusion Service and Cell Therapy Unit of Fondazione IRCCS, S. Matteo, 27100 Pavia, Italy
| | - Cesare Perotti
- Immunohaematology and Transfusion Service and Cell Therapy Unit of Fondazione IRCCS, S. Matteo, 27100 Pavia, Italy
| | - Dalila Miele
- Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy
| | - Barbara Vigani
- Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy
| | - Franca Ferrari
- Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy
| |
Collapse
|
|
24
|
Bernabei F, Roda M, Buzzi M, Pellegrini M, Giannaccare G, Versura P. Blood-Based Treatments for Severe Dry Eye Disease: The Need of a Consensus. J Clin Med 2019; 8:E1478. [PMID: 31533289 PMCID: PMC6780616 DOI: 10.3390/jcm8091478] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 09/05/2019] [Accepted: 09/12/2019] [Indexed: 01/08/2023] Open
Abstract
The use of blood-based eye drops as therapy for various diseases of the ocular surface has become increasingly popular in ophthalmic practice during recent years. The rationale for their use is based on the promotion of cellular proliferation and migration thanks to the supply of metabolically active substances, in particular growth factors. Blood-derived eye drops have been used for the treatment of several ocular surface disorders, such as dry eye disease, corneal ulcer, persistent epithelial defect, neurotrophic keratitis, ocular surface burn, recurrent corneal erosion, and limbal stem-cell deficiency. Both autologous (from patients themselves) and heterologous (from adult donors or from cord blood sampled at birth)-derived products exist, and each source has specific pros and cons. Despite an extensive literature, several issues are still under debate and the aim of this manuscript is to review the indications, preparation methods and storage, characterization of content, rationale for clinical outcomes, patient stratification, length of treatment, and rationale for repeated treatments at disease relapse. A rationale based on a "5 Ws and 2 Hs" protocol is proposed as a way of thinking, with the attempt to clarify Who, Why, When, Where, What, and How to use these treatment options.
Collapse
Affiliation(s)
- Federico Bernabei
- Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy.
| | - Matilde Roda
- Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy.
| | - Marina Buzzi
- Emilia Romagna Cord Blood Bank-Transfusion Service, S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy.
| | - Marco Pellegrini
- Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy.
| | - Giuseppe Giannaccare
- Department of Ophthalmology, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy.
| | - Piera Versura
- Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy.
| |
Collapse
|
|
25
|
Ogawa Y. Sjögren's Syndrome, Non-Sjögren's Syndrome, and Graft-Versus-Host Disease Related Dry Eye. Invest Ophthalmol Vis Sci 2019; 59:DES71-DES79. [PMID: 30481809 DOI: 10.1167/iovs.17-23750] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
I have reviewed available literature on dry eye related to Sjögren's syndrome (SS), non-Sjögren's syndrome (non-SS), and graft-versus-host disease (GVHD) to examine aqueous tear deficient dry eye as a subtype of dry eye. This section will focus on clinical studies regarding those subtypes of dry eye. I searched the PubMed database from 1990-2017 for discussion of clinical features, diagnostic criteria, and risk factors of SS, non-SS, and GVHD-related dry eye. In addition, therapeutic options for each subtype of dry eye are described. Although the clinical presentations of SS and chronic graft-versus-host disease (cGVHD) are similar, ocular surface fibrotic changes are characteristic of ocular GVHD but not SS- or non-SS-related dry eye. Recently, diagnostic criteria for each disease have been proposed and include the American College of Rheumatology/European League Against Rheumatism (ACR-EULAR) for SS and the International Chronic Ocular GVHD consensus criteria. Although there has been gradual progress, there are currently no specific therapies and few approved treatment options for these intractable diseases, including SS and GVHD. As judged by the findings, these subtypes of dry eye are different clinical entities from simple dry eye. Therefore, novel therapies, specific to these subtypes of dry eye, may be required in the future.
Collapse
Affiliation(s)
- Yoko Ogawa
- Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan
| |
Collapse
|
|
26
|
Zamani M, Yaghoubi Y, Movassaghpour A, Shakouri K, Mehdizadeh A, Pishgahi A, Yousefi M. Novel therapeutic approaches in utilizing platelet lysate in regenerative medicine: Are we ready for clinical use? J Cell Physiol 2019; 234:17172-17186. [PMID: 30912141 DOI: 10.1002/jcp.28496] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 02/18/2019] [Accepted: 02/20/2019] [Indexed: 12/13/2022]
Abstract
Hemoderivative materials are used to treat different diseases. These derivatives include platelet-rich plasma, serum, platelet gel, and platelet lysate (PL). Among them, PL contains more growth factors than the others and its production is inexpensive and easy. PL is one of the proper sources of platelet release factors. It is used in cells growth and proliferation and is a good alternative to fetal bovine serum. In recent years, the clinical use of PL has gained more appeal by scientists. PL is a solution saturated by growth factors, proteins, cytokines, and chemokines and is administered to treat different diseases such as wound healing, bone regeneration, alopecia, oral mucositis, radicular pain, osteoarthritis, and ocular diseases. In addition, it can be used in cell culture for cell therapy and tissue transplantation purposes. Platelet-derived growth factor, fibroblast growth factor, insulin-like growth factor, transforming growth factor β, and vascular endothelial growth factor are key PL growth factors playing a major role in cell proliferation, wound healing, and angiogenesis. In this paper, we scrutinized recent advances in using PL and PL-derived growth factors to treat diseases and in regenerative medicine, and the ability to replace PL with other hemoderivative materials.
Collapse
Affiliation(s)
- Majid Zamani
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Yoda Yaghoubi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Immunology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Aliakbar Movassaghpour
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Hematology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Kazem Shakouri
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Mehdizadeh
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Pishgahi
- Department of Hematology, Tabriz University of Medical Sciences, Tabriz, Iran.,Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Yousefi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Immunology, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
|
27
|
Mawardi H, Hashmi SK, Elad S, Aljurf M, Treister N. Chronic graft‐versus‐host disease: Current management paradigm and future perspectives. Oral Dis 2018; 25:931-948. [DOI: 10.1111/odi.12936] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 07/04/2018] [Accepted: 07/04/2018] [Indexed: 12/14/2022]
Affiliation(s)
- Hani Mawardi
- Faculty of Dentistry King AbdulAziz University Jeddah Kingdom of Saudi Arabia
- AlFarabi Private College Jeddah Kingdom of Saudi Arabia
| | - Shahrukh K. Hashmi
- Department of Medicine Mayo Clinic Rochester Minnesota
- Oncology Center KFSHRC Riyadh Kingdom of Saudi Arabia
| | - Sharon Elad
- Department of Dentistry University of Rochester Rochester New York
| | | | - Nathaniel Treister
- Division of Oral Medicine and Dentistry, Brigham and Women's Hospital Boston Massachusetts
- Department of Oral Medicine, Infection and Immunity Harvard School of Dental Medicine Boston Massachusetts
| |
Collapse
|
|
28
|
Buzzi M, Versura P, Grigolo B, Cavallo C, Terzi A, Pellegrini M, Giannaccare G, Randi V, Campos EC. Comparison of growth factor and interleukin content of adult peripheral blood and cord blood serum eye drops for cornea and ocular surface diseases. Transfus Apher Sci 2018; 57:549-555. [PMID: 29929885 DOI: 10.1016/j.transci.2018.06.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 05/31/2018] [Accepted: 06/05/2018] [Indexed: 11/15/2022]
Abstract
INTRODUCTION Various blood-derived products have been proposed for the topical treatment of ocular surface diseases. The aim of the study was to compare the different content of Growth Factors (GFs) and Interleukins (ILs) in peripheral blood (PB-S) and Cord Blood (CB-S) sera. MATERIALS AND METHODS Sera were obtained from 105 healthy adult donors (PB-S) and 107 umbilical/placental veins at the time of delivery (CB-S). The levels of epithelial-GF (EGF), fibroblast-GF (FGF), platelet-derived-GF (PDGF), insulin-GF (IGF), transforming-GF alpha (TGF-α,) and beta 1-2-3 (TGF-β1-β2-β3), vascular endothelial-GF (VEGF), nerve-GF (NGF), Interleukin (IL)-1β,IL-4,IL-6,IL-10, and IL-13 were assessed by Bio-Plex Protein Array System (Bio-Rad Laboratories, CA, USA). The Mann-Whitney test for unpaired data was applied to compare GFs and ILs levels in the two sources. The associations among each GF/IL level and the obstetric data for CB-S and hematological characteristics for PB-S were also investigated. RESULTS The levels of EGF, TGF-α, TGF-β2, FGF, PDGF, VEGF, NGF, IL-1B, IL-4, IL-6, IL-10, and IL-13 were significantly higher in CB-S compared to PB-S. Conversely, the levels of IGF-1, IGF-2, and TGF-β1 were significantly higher in PB-S. The female sex and the weight of the child showed a significant association in predicting EGF and PDGF levels. CONCLUSION A significantly different content in those GFs and ILs was demonstrated in the two blood sources. Since each GF/IL selectively regulates different cellular processes involved in corneal healing, the use of PB-S or CB-S should be chosen on the basis of the cellular mechanism to be promoted in each clinical case.
Collapse
Affiliation(s)
- M Buzzi
- Emilia Romagna Cord Blood Bank-Transfusion Service, S.Orsola-Malpighi Teaching Hospital, Bologna, Italy
| | - P Versura
- Ophthalmology Unit, DIMES, Alma Mater Studiorum University of Bologna and S.Orsola-Malpighi Teaching Hospital, Bologna, Italy.
| | - B Grigolo
- RAMSES Laboratory, Department of Research & Innovation, Istituto Ortopedico Rizzoli, Bologna, Italy
| | - C Cavallo
- RAMSES Laboratory, Department of Research & Innovation, Istituto Ortopedico Rizzoli, Bologna, Italy
| | - A Terzi
- Emilia Romagna Cord Blood Bank-Transfusion Service, S.Orsola-Malpighi Teaching Hospital, Bologna, Italy
| | - M Pellegrini
- Ophthalmology Unit, DIMES, Alma Mater Studiorum University of Bologna and S.Orsola-Malpighi Teaching Hospital, Bologna, Italy
| | - G Giannaccare
- Ophthalmology Unit, DIMES, Alma Mater Studiorum University of Bologna and S.Orsola-Malpighi Teaching Hospital, Bologna, Italy
| | - V Randi
- Emilia Romagna Cord Blood Bank-Transfusion Service, S.Orsola-Malpighi Teaching Hospital, Bologna, Italy
| | - E C Campos
- Ophthalmology Unit, DIMES, Alma Mater Studiorum University of Bologna and S.Orsola-Malpighi Teaching Hospital, Bologna, Italy
| |
Collapse
|
|
29
|
Baigger A, Eicke D, Yuzefovych Y, Pogozhykh D, Blasczyk R, Figueiredo C. Characterization of induced pluripotent stem cell-derived megakaryocyte lysates for potential regenerative applications. J Cell Mol Med 2018; 22:4545-4549. [PMID: 29893509 PMCID: PMC6111809 DOI: 10.1111/jcmm.13698] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 04/17/2018] [Indexed: 12/14/2022] Open
Abstract
Recently, platelet‐derived growth factors present in lysates became an extreme interest in the field of regenerative medicine such as in wound healing and as substitutes to foetal bovine serum in xeno‐free cell culture systems. However, the generation of such platelet lysates completely depends on the availability of platelet donors. In this study, the possibility to use in vitro‐generated megakaryocytes derived from induced pluripotent stem cells (iPSCs) as a cell source for typical platelet growth factors was investigated. Therefore, the presence and levels of those factors were characterized in in vitro‐produced megakaryocytes. In comparison with platelets, in vitro‐generated megakaryocytes showed a multifold increased content in transcript and protein levels of typical platelet growth factors including platelet‐derived growth factors (PDGFs), transforming growth factor (TGF)‐1β, vascular endothelial cell factor (VEGF)‐A, epidermal growth factor (EGF), insulin‐like growth factor (IGF)‐1 and tissue factor (TF). Hence, iPSC‐derived megakaryocytes may serve as an efficient cell source for a donor‐independent generation of growth factor‐rich lysates with a broad application potential in innovative cell culture systems and regenerative therapies.
Collapse
Affiliation(s)
- Anja Baigger
- Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany
| | - Dorothee Eicke
- Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany
| | - Yuliia Yuzefovych
- Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany
| | - Denys Pogozhykh
- Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany
| | - Rainer Blasczyk
- Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany
| | | |
Collapse
|
|
30
|
Bojanic I, Stipetic MM, Pulanic D, Desnica L, Mazic S, Cepulic BG, Seiwerth RS, Vrhovac R, Nemet D, Pavletic SZ. Autologous blood as a source of platelet gel for the effective and safe treatment of oral chronic graft-versus-host disease. Transfusion 2018; 58:1494-1499. [PMID: 29542126 PMCID: PMC6786782 DOI: 10.1111/trf.14594] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 12/13/2017] [Accepted: 01/22/2018] [Indexed: 12/27/2022]
Abstract
BACKGROUND Oral chronic graft-versus-host disease (cGvHD) impairs oral function and patients' quality of life. Some lesions are refractory to local and systemic immunosuppressive therapy, and new therapeutic modalities are required. The aim of the study was to assess the efficacy and safety of topical application of autologous platelet gel (PG) in patients with oral cGvHD. STUDY DESIGN AND METHODS PG was prepared from autologous blood and applied on ulcerous lesions using an automated system. The oral cGvHD was assessed using the 273-point Oral Mucositis Rating Scale (OMRS) prior and after completion of the PG treatment. The overall response to treatment of particular topography expressed as the total score on OMRS was compared to total score on National Institutes of Health cGvHD Oral Mucosal Score (NIH OMS). The pain intensity was measured by the Numeric Pain Rating Scale (NRS). RESULTS In five patients, 12 autologous blood collections were performed; median 3 (range 1-3) per patient, and 26 PG applications were performed; median 6 (range 2-8) per patient. PG applications reduced lesions in oral cGvHD: median OMRS total score was reduced for 43.2% (range 9.6%-47.3%), and median NIH OMS total score for 27.3% (range 20.0%-50.0%) from baseline values. Median of pain intensity reduction on NRS scale was 57.1% (range 50%-100%). No side effects were observed. CONCLUSION Application of autologous PG in oral cGvHD showed as an efficient and safe treatment option for patients who do not respond to standard local treatment.
Collapse
Affiliation(s)
- Ines Bojanic
- Department of Transfusion Medicine and Transplantation Biology, University Hospital Center Zagreb
| | - Marinka Mravak Stipetic
- Department of Dental Medicine, University Hospital Center Zagreb
- University of Zagreb, School of Dental Medicine
| | - Drazen Pulanic
- Division of Hematology, Department of Internal Medicine, University Hospital Center Zagreb
- University of Zagreb, School of Medicine, Zagreb, Croatia
- J. J. Strossmayer University of Osijek, Faculty of Medicine Osijek, Osijek, Croatia
| | - Lana Desnica
- Division of Hematology, Department of Internal Medicine, University Hospital Center Zagreb
| | - Sanja Mazic
- Department of Transfusion Medicine and Transplantation Biology, University Hospital Center Zagreb
| | - Branka Golubic Cepulic
- Department of Transfusion Medicine and Transplantation Biology, University Hospital Center Zagreb
- University of Zagreb, School of Medicine, Zagreb, Croatia
| | | | - Radovan Vrhovac
- Division of Hematology, Department of Internal Medicine, University Hospital Center Zagreb
- University of Zagreb, School of Medicine, Zagreb, Croatia
| | - Damir Nemet
- Division of Hematology, Department of Internal Medicine, University Hospital Center Zagreb
- University of Zagreb, School of Medicine, Zagreb, Croatia
- J. J. Strossmayer University of Osijek, Faculty of Medicine Osijek, Osijek, Croatia
| | - Steven Z. Pavletic
- National Cancer Institute, Center for Cancer Research, NIH, Bethesda, Maryland
| |
Collapse
|
|
31
|
Association of Alpha Tocopherol and Ag Sulfadiazine Chitosan Oleate Nanocarriers in Bioactive Dressings Supporting Platelet Lysate Application to Skin Wounds. Mar Drugs 2018; 16:md16020056. [PMID: 29425164 PMCID: PMC5852484 DOI: 10.3390/md16020056] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2018] [Revised: 01/31/2018] [Accepted: 02/06/2018] [Indexed: 12/25/2022] Open
Abstract
Chitosan oleate was previously proposed to encapsulate in nanocarriers some poorly soluble molecules aimed to wound therapy, such as the anti-infective silver sulfadiazine, and the antioxidant α tocopherol. Because nanocarriers need a suitable formulation to be administered to wounds, in the present paper, these previously developed nanocarriers were loaded into freeze dried dressings based on chitosan glutamate. These were proposed as bioactive dressings aimed to support the application to wounds of platelet lysate, a hemoderivative rich in growth factors. The dressings were characterized for hydration capacity, morphological aspect, and rheological and mechanical behavior. Although chitosan oleate nanocarriers clearly decreased the mechanical properties of dressings, these remained compatible with handling and application to wounds. Preliminary studies in vitro on fibroblast cell cultures demonstrated good compatibility of platelet lysate with nanocarriers and bioactive dressings. An in vivo study on a murine wound model showed an accelerating wound healing effect for the bioactive dressing and its suitability as support of the platelet lysate application to wounds.
Collapse
|
|
32
|
Cid J, Carbassé G, Cid-Caballero M, López-Púa Y, Alba C, Perea D, Lozano M. The Barcelona Hospital Clínic therapeutic apheresis database. J Clin Apher 2017; 33:259-264. [DOI: 10.1002/jca.21587] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Revised: 08/03/2017] [Accepted: 09/06/2017] [Indexed: 12/26/2022]
Affiliation(s)
- Joan Cid
- Apheresis Unit, Department of Hemotherapy and Hemostasis; ICMHO, IDIBAPS, Hospital Clínic, University of Barcelona; Barcelona Spain
| | - Gloria Carbassé
- Apheresis Unit, Department of Hemotherapy and Hemostasis; ICMHO, IDIBAPS, Hospital Clínic, University of Barcelona; Barcelona Spain
| | | | - Yolanda López-Púa
- Department of Preventive Medicine and Epidemiology; ICMiD, Hospital Clínic, University of Barcelona, ISGlobal; Barcelona Spain
| | - Cristina Alba
- Apheresis Unit, Department of Hemotherapy and Hemostasis; ICMHO, IDIBAPS, Hospital Clínic, University of Barcelona; Barcelona Spain
| | - Dolores Perea
- Apheresis Unit, Department of Hemotherapy and Hemostasis; ICMHO, IDIBAPS, Hospital Clínic, University of Barcelona; Barcelona Spain
| | - Miguel Lozano
- Apheresis Unit, Department of Hemotherapy and Hemostasis; ICMHO, IDIBAPS, Hospital Clínic, University of Barcelona; Barcelona Spain
| |
Collapse
|
|
33
|
Baigger A, Blasczyk R, Figueiredo C. Towards the Manufacture of Megakaryocytes and Platelets for Clinical Application. Transfus Med Hemother 2017. [PMID: 28626367 DOI: 10.1159/000477261] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Platelet transfusions are used in standard clinical practice to prevent hemorrhage in patients suffering from thrombocytopenia or platelet dysfunctions. Recently, a constant rise on the demand of platelets for transfusion has been registered. This may be associated with several factors including demographic changes, population aging as well as incidence and prevalence of hematological diseases. In addition, platelet-regenerative properties have been started to be exploited in different areas such as tissue remodeling and anti-cancer therapies. These new applications are also expected to increase the future demand on platelets. Thus, in vitro generated platelets may constitute a highly desirable alternative to meet the rising demand on platelets. Several factors have been considered in the road trip of producing in vitro megakaryocytes and platelets for clinical application. From selection of the cell source, differentiation protocols and culture conditions to the design of optimal bioreactors, several strategies have been proposed to maximize production yields while preserving functionality. This review summarizes new advances in megakaryocyte and platelet differentiation and their production upscaling.
Collapse
Affiliation(s)
- Anja Baigger
- Institute for Transfusion Medicine, Hanover Medical School, Hanover, Germany
| | - Rainer Blasczyk
- Institute for Transfusion Medicine, Hanover Medical School, Hanover, Germany
| | | |
Collapse
|
|
34
|
Milner MS, Beckman KA, Luchs JI, Allen QB, Awdeh RM, Berdahl J, Boland TS, Buznego C, Gira JP, Goldberg DF, Goldman D, Goyal RK, Jackson MA, Katz J, Kim T, Majmudar PA, Malhotra RP, McDonald MB, Rajpal RK, Raviv T, Rowen S, Shamie N, Solomon JD, Stonecipher K, Tauber S, Trattler W, Walter KA, Waring GO, Weinstock RJ, Wiley WF, Yeu E. Dysfunctional tear syndrome: dry eye disease and associated tear film disorders - new strategies for diagnosis and treatment. Curr Opin Ophthalmol 2017; 27 Suppl 1:3-47. [PMID: 28099212 PMCID: PMC5345890 DOI: 10.1097/01.icu.0000512373.81749.b7] [Citation(s) in RCA: 141] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Dysfunctional tear syndrome (DTS) is a common and complex condition affecting the ocular surface. The health and normal functioning of the ocular surface is dependent on a stable and sufficient tear film. Clinician awareness of conditions affecting the ocular surface has increased in recent years because of expanded research and the publication of diagnosis and treatment guidelines pertaining to disorders resulting in DTS, including the Delphi panel treatment recommendations for DTS (2006), the International Dry Eye Workshop (DEWS) (2007), the Meibomian Gland Dysfunction (MGD) Workshop (2011), and the updated Preferred Practice Pattern guidelines from the American Academy of Ophthalmology pertaining to dry eye and blepharitis (2013). Since the publication of the existing guidelines, new diagnostic techniques and treatment options that provide an opportunity for better management of patients have become available. Clinicians are now able to access a wealth of information that can help them obtain a differential diagnosis and treatment approach for patients presenting with DTS. This review provides a practical and directed approach to the diagnosis and treatment of patients with DTS, emphasizing treatment that is tailored to the specific disease subtype as well as the severity of the condition.
Collapse
Affiliation(s)
- Mark S. Milner
- Yale University School of Medicine, New Haven
- The Eye Center of Southern Connecticut, Hamden, Connecticut
- Mark S. Milner, Kenneth A. Beckman, and Jodi I. Luchs are co-chairs
| | - Kenneth A. Beckman
- Ohio State University, Columbus
- Comprehensive Eye Care of Central Ohio, Westerville, Ohio
- Mark S. Milner, Kenneth A. Beckman, and Jodi I. Luchs are co-chairs
| | - Jodi I. Luchs
- Hofstra Northwell School of Medicine, Hempstead
- South Shore Eye Care, Wantagh, New York
- Mark S. Milner, Kenneth A. Beckman, and Jodi I. Luchs are co-chairs
| | | | - Richard M. Awdeh
- Bascom Palmer Eye Institute, Florida International University, and Center for Excellence in Eye Care, Miami, Florida
| | - John Berdahl
- Vance Thompson Vision, Sioux Falls, South Dakota
| | - Thomas S. Boland
- Northeastern Eye Institute, Scranton
- Commonwealth Medical College, Scranton, Pennsylvania
| | - Carlos Buznego
- Bascom Palmer Eye Institute, Florida International University, and Center for Excellence in Eye Care, Miami, Florida
| | | | - Damien F. Goldberg
- Jules Stein Eye Institute, Los Angeles
- Wolstan & Goldberg Eye Associates, Torrance, California
| | | | - Raj K. Goyal
- Rush University Medical Center, Chicago
- Chicago Eye Specialists
| | | | - James Katz
- Midwest Center for Sight, Des Plaines, Illinois
| | - Terry Kim
- Duke Eye Center, Durham, North Carolina
| | - Parag A. Majmudar
- Rush University Medical Center, Chicago
- Chicago Cornea Consultants, Ltd, Hoffman Estates, Illinois
| | - Ranjan P. Malhotra
- Washington University Department of Ophthalmology and Ophthalmology Associates, St. Louis, Missouri
| | - Marguerite B. McDonald
- NYU Langone Medical Center, New York, New York
- Tulane University School of Medicine, New Orleans, Louisiana
- Ophthalmic Consultants of Long Island, Lynbrook, New York
- The Center for Ocular Surface Excellence of New Jersey, Woodland Park, New Jersey
| | - Rajesh K. Rajpal
- Georgetown University Medical Center, George Washington University Medical Center, Washington, DC
| | - Tal Raviv
- New York Eye and Ear Infirmary of Mount Sinai and Eye Center of New York, New York, New York
| | - Sheri Rowen
- NVision EyeCenters of Newport Beach, Newport Beach, California
- University of Maryland, Baltimore, Maryland
| | - Neda Shamie
- Advanced Vision Care, Century City, California
- Keck School of Medicine, University of Southern California, Los Angeles
| | | | - Karl Stonecipher
- University of North Carolina and TLC Laser Eye Centers, Greensboro, North Carolina
| | | | - William Trattler
- Bascom Palmer Eye Institute, Florida International University, and Center for Excellence in Eye Care, Miami, Florida
| | | | - George O. Waring
- Storm Eye Institute and Magill Vision Center, Medical University of South Carolina, Charleston
- Clemson University, Mt. Pleasant, South Carolina
| | - Robert J. Weinstock
- University of South Florida, Tampa
- The Eye Institute of West Florida, Largo, Florida
| | - William F. Wiley
- Cleveland Eye Clinic, Clear Choice Custom LASIK Center, Brecksville, Ohio
| | - Elizabeth Yeu
- Eastern Virginia Medical School and Virginia Eye Consultants, Norfolk, Virginia, USA
| |
Collapse
|