Loading

Clinical Research in Pulmonology

Cell-Based Therapy for Lung Diseases: Past, Present and Future

Editorial | Open Access

  • 1. Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Acute Lung Injury Center of Excellence, Division of Pulmonary Allergy and Critical Care Medicine, School of Medicine, McGowan Institute for Regenerative Medicine. University of Pittsburgh, USA
+ Show More - Show Less
Corresponding Authors
Mauricio Rojas, Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Acute Lung Injury Center of Excellence, Division of Pulmonary Allergy and Critical Care Medicine, School of Medicine, McGowan Institute for Regenerative Medicine. University of Pittsburgh, Pittsburgh, USA
Citation

Rojas M (2013) Cell-Based Therapy for Lung Diseases: Past, Present and Future. Clin Res Pulmonol 1: 1006.

Editorial

Numerous lung diseases have high morbidity and mortality rates and there are no cures or treatments apart from lung transplantation. In United States, respiratory diseases kill more than 400,000 individuals each year and significantly reduce quality of life for millions more not only impacting the patient but all the members of the family. The National institute of Health estimated that in 2009 the annual cost of providing healthcare related to all respiratory conditions, excluding lung cancer, was $113 billion [1]. These choices are unacceptable for the society and the patients, so responding to the desperate need for new therapies, research has turned toward stem cells and the ways by which they can be use to treat pulmonary diseases. Cellbased therapies are currently an area of intense research, and preliminary data generated by many groups, including ours, foreseeing the translation of successful pre-clinical studies into therapies were we expect them to be not only effective for multiple lung diseases but also safe to the patients.

Our group has extensive experience on bone marrow derived mesenchymal stem cells. Bone marrow derived stem cells can be divided in two groups: hematopoietic stem cells (HSC) and mesenchymal stromal stem cells (MSC). HSC have been the most successful form of cell therapy, transplant of whole bone marrow or HSC have been use in clinic since the 50s and 60s for the repopulation of the different cell types present in the blood [2-6]. Bone marrow derived mesenchymal stromal cells (B-MSCs) were first described in the early 1970s by Friedenstein and collaborators [7-10], as clonal, plastic adherent cells capable of differentiating into cells of mesenchymal origin. In vivo, these cells are also required to support hematopoiesis providing extracellular matrix, cytokines, and growth factors to the HSC [11-13].

Characterization, isolation and study of the basic biology of B-MSCs has been a complicated issue since there are no specific cell surface marker that can be use to not only isolate the cells but also demonstrate, in vivo, their biological activity. All the therapeutic properties have been demonstrated for B-MSC are after in vitro isolation and expansion and subsequent infusion. Enrichment of B-MSCs from bone marrow suspensions can be achieved by selecting a plastic-adherent population that expresses neither hematopoietic nor endothelial cell surface markers but is positive for the expression of stromal markers [14]. The criterion for establishing B-MSC phenotype is to use adherent cells that (i) express CD44, CD73, CD90 and CD105, (ii) lack the expression of hematopoietic markers like CD45, CD34 and CD31 and finally (iii) a multilineage differentiation assay to confirm their plasticity by the ability of the cells to differentiate into adipocytes, osteocytes, and chondrocytes [15-17].

Lung diseases can be divided into two groups: acute and chronic. Cell based therapy with B-MSCs have been demonstrated to be effective preventing the progression and inducing lung repair in both groups.

Acute lung injury or acute respiratory distress syndrome (ARDS) is a common complication in the intensive care unit. Even though extensive research has been done in the last years, the ARDS mortality rate still stands as high as 40% [18], and the only current treatments are supportive and include lung-protective ventilation together with a fluid conservative strategy. Since the publication of our original work in 2007 [19] we defined the beneficial effects of the systemic administration of B-MSC to control ARDS mainly by their anti-inflammatory properties. Multiple groups have obtained similar observations where the protective effect has been demonstrated in different animal models of ARDS and human ex-vivo lungs [20-25].

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by deposition of collagen resulting on scarring of the lung [26,27]. The current most accepted animal model of pulmonary fibrosis consist in the intratracheal instillation of bleomycin an anticancer agent commonly used in the treatment of Hodgkin’s lymphoma and testicular cancer [28- 30] which has a secondary effect of pulmonary fibrosis. Since the work published by Ortiz and subsequently by our group [31,32], we demonstrated that B-MSC infusion caused a decrease in the deposition of lung matrix metalloproteinase and lung collagen. Interestingly, B-MSCs effect was found to be insufficient when cell were infused late at 7 days after bleomycin challenge, highlighting the variety of factors that interact to play a role in B-MSC-based therapy. 

For a better understanding of the protective abilities of B-MSCs and by which mechanisms they operate, our group administered bleomycin to myelosuppressed mice and to mice with normal, intact bone marrow. A subgroup of mice within each group received an additional infusion of (GFP)-positive MSCs 6 hours after bleomycin treatment. MSC infusion proved to confer a significant survival benefit in myelosuppressed bleomycintreated mice from 80% mortality to 0%.

There is recent report on the safety of the use of B-MSC on chronic obstructive pulmonary disease or COPD, in which the authors were able to demonstrate the safety on the intravenous injection of B-MSC on this group of patients. Because the study was not designed to evaluate efficacy, we do not know if B-MSCs have a beneficial effect on COPD [33].

Finally, for patients with end-stage pulmonary disease where treating the disease is no longer viable, transplantation is the only feasible option. Transplants carry great risks and one of the major complications is the development of obliterative bronchiolitis (OB), accounting for almost 50% of the mortality of lung recipients within five years of transplantation [34]. Cellular therapy to treat OB has been promising in some animal studies. We recently demonstrated that in a murine model of heterotopic tracheal transplantation that systemic administration of B-MSCs inhibits inflammation and fibrosis, preventing the occlusion of the transplanted tracheas [35], demonstrating the viability of cell therapy options in attenuating the morbid complications of lung transplants.

The protective effects of B-MSCs are attributed to several mechanisms including secretion of anti-inflammatory cytokines IL-10 and TGF-a, KGF, mitochondrial transfer, elaboration of antibacterial peptides and more recently by transfer of micro RNAs inducing macrophage activation [36-39]. Additionally, it has been demonstrated that B-MSCs reduced mortality and organ injury when delivered systemically in a model of bacteremia and septic shock due to B-MSCs enhanced bacterial clearance consequent to increased phagocytosis of host immune cells [40]. As a result of these most recent studies, B-MSCs are increasingly recognized for having complex interactions with the host immune system and share properties with cells of the innate immune system. Given the pleiotropic mechanisms and their potential as therapy of multiple lung diseases, there is a considerable interest in initiating translational studies for the use of B-MSC in the pulmonary field.

Our group believes that in the next few years, to develop an effective cell-based therapy in the lung —with B-MSCs in particular- our research will need to focus on mechanism that can affect B-MSC function. In our experience, the two most important facts are on effect of aging on B-MSCs function and the novel posttranscriptional mechanisms driving regulation of the gene expression as microRNA, RNAlinks and DNA methylation. Little is known about the consequences that these different elements can have on the B-MSC function, questions like, are these elements synergistic or totally independent? Can they explain the age differences of the incidence of different lung diseases? All of these are questions that remain unanswered. Understanding their role on B-MSCs function can help enhance their activity by selecting the most appropriate type of cells to be use in an eventual cell therapy.

In summary, it is our strong believe that the use of cellbased therapy, and specifically non-hematopoietic stem cells, is going to be real alternative to treat multiple lung diseases and since B-MSCs have such a high therapeutic potential that can be navigated in different ways, it is imperative to focus on each and every therapeutic aspect that B-MSCs can hold, including appropriate cell type and clinical trials to determine their safety in distinct types of patients.

REFERENCES

1. Schraufnagel DE. Breathing in America : diseases, progress, and hope. [New York]: American Thoracic Society; 2010.

2. Thomas ED, Clift RA, Fefer A, Storb R, Buckner CD. When should you consider a bone marrow transplant? Med Times. 1978; 106: 1-15.

3. THOMAS ED, LOCHTE HL Jr, LU WC, FERREBEE JW. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N Engl J Med. 1957; 257: 491-6.

4. THOMAS ED, LOCHTE HL Jr. Studies on the biochemical defect of pernicious anemia. I. In vitro observations on oxygen consumption, heme synthesis and deoxyribonucleic acid synthesis by pernicious anemia bone marrow. J Clin Invest. 1958; 37: 166-71.

5. THOMAS ED, ASHLEY CA, LOCHTE HL Jr, JARETZKI A 3rd, SAHLER OD, FERREBEE JW. Homografts of bone marrow in dogs after lethal totalbody radiation. Blood. 1959; 14: 720-36.

6. FERREBEE JW, THOMAS ED. Present status of bone marrow transplantation. Pediatr Clin North Am. 1962; 9: 851-3.

7. Friedenstein AJ, Deriglasova UF, Kulagina NN, Panasuk AF, Rudakowa SF, Luriá EA, et al. Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method. Exp Hematol. 1974; 2: 83-92.

8. Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation. 1974; 17: 331-40.

9. Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 1970; 3: 393-403.

10. Friedenstein A, Kuralesova AI. Osteogenic precursor cells of bone marrow in radiation chimeras. Transplantation. 1971; 12: 99-108.

11. Roberts EW, Deonarine A, Jones JO, Denton AE, Feig C, Lyons SK, et al. Depletion of stromal cells expressing fibroblast activation protein-α from skeletal muscle and bone marrow results in cachexia and anemia. J Exp Med. 2013; 210: 1137-51.

12. Nakamura-Ishizu A, Suda T. Hematopoietic stem cell niche: an interplay among a repertoire of multiple functional niches. Biochim Biophys Acta. 2013; 1830: 2404-9.

13. Law S, Chaudhuri S. Mesenchymal stem cell and regenerative medicine: regeneration versus immunomodulatory challenges. Am J Stem Cells. 2013; 2: 22-38.

14. Singer NG, Caplan AI. Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol. 2011; 6: 457-78.

15. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8: 315-7.

16. Weiss DJ, Bertoncello I, Borok Z, Kim C, Panoskaltsis-Mortari A, Reynolds S, et al. Stem cells and cell therapies in lung biology and lung diseases. Proc Am Thorac Soc. 2011; 8: 223-72.

17. Weiss DJ, Kolls JK, Ortiz LA, Panoskaltsis-Mortari A, Prockop DJ. Stem cells and cell therapies in lung biology and lung diseases. Proc Am Thorac Soc. 2008; 5: 637-67.

18. Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, et al. Incidence and outcomes of acute lung injury. N Engl J Med. 2005; 353: 1685-93.

19. Xu J, Woods CR, Mora AL, Joodi R, Brigham KL, Iyer S, et al. Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice. Am J Physiol Lung Cell Mol Physiol. 2007; 293: 131-41.

20. Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol. 2007; 179: 1855-63.

21. Cribbs SK, Matthay MA, Martin GS. Stem cells in sepsis and acute lung injury. Crit Care Med. 2010; 38: 2379-85.

22. Fang X, Neyrinck AP, Matthay MA, Lee JW. Allogeneic human mesenchymal stem cells restore epithelial protein permeability in cultured human alveolar type II cells by secretion of angiopoietin-1. J Biol Chem. 2010; 285: 26211-22.

23. Lee JW, Fang X, Gupta N, Serikov V, Matthay MA. Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung. Proc Natl Acad Sci U S A. 2009; 106: 16357-62.

24. Matthay MA, Goolaerts A, Howard JP, Lee JW. Mesenchymal stem cells for acute lung injury: preclinical evidence. Crit Care Med. 2010; 38: S569-73.

25. Serikov VB, Mikhaylov VM, Krasnodembskay AD, Matthay MA. Bone marrow-derived cells participate in stromal remodeling of the lung following acute bacterial pneumonia in mice. Lung. 2008; 186: 179- 90.

26. Strange C, Highland KB. Pulmonary hypertension in interstitial lung disease. Curr Opin Pulm Med. 2005; 11: 452-5.

27. Polomis D, Runo JR, Meyer KC. Pulmonary hypertension in interstitial lung disease. Curr Opin Pulm Med. 2008; 14: 462-9.

28. Yuasa T, Yoshida T, Wakabayashi Y, Kataoka A, Narita M, Yoshiki T, et al. Successful treatment of disseminated extragonadal germ cell cancer with intensive conventional chemotherapy after first-line highdose chemotherapy. Int J Clin Oncol. 2006; 11: 60-3.

29. Kawai K, Akaza H. Bleomycin-induced pulmonary toxicity in chemotherapy for testicular cancer. Expert Opin Drug Saf. 2003; 2: 587-96.

30. Bower M, Newlands ES, Holden L, Rustin GJ, Begent RH. Treatment of men with metastatic non-seminomatous germ cell tumours with cyclical POMB/ACE chemotherapy. Ann Oncol. 1997; 8: 477-83.

31. Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A. 2003; 100: 8407-11.

32. Rojas M, Xu J, Woods CR, Mora AL, Spears W, Roman J, et al. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol. 2005; 33: 145-52.

33. Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP. A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest. 2013; 143: 1590-8.

34. Christie JD, Edwards LB, Kucheryavaya AY, Benden C, Dipchand AI, Dobbels F, et al. The Registry of the International Society for Heart and Lung Transplantation: 29th adult lung and heart-lung transplant report-2012. J Heart Lung Transplant. 2012; 31: 1073-86.

35. Grove DA, Xu J, Joodi R, Torres-Gonzales E, Neujahr D, Mora AL, et al. Attenuation of early airway obstruction by mesenchymal stem cells in a murine model of heterotopic tracheal transplantation. J Heart Lung Transplant. 2011; 30: 341-50.

36. Cárdenes N, Cáceres E, Romagnoli M, Rojas M. Mesenchymal stem cells: a promising therapy for the acute respiratory distress syndrome. Respiration. 2013; 85: 267-78.

37. Kapetanaki MG, Mora AL, Rojas M. Influence of age on wound healing and fibrosis. J Pathol. 2013; 229: 310-22.

38. Matthay MA, Goolaerts A, Howard JP, Lee JW. Mesenchymal stem cells for acute lung injury: preclinical evidence. Crit Care Med. 2010; 38: S569-73.

39. Matthay MA, Thompson BT, Read EJ, McKenna DH Jr, Liu KD, Calfee CS, et al. Therapeutic potential of mesenchymal stem cells for severe acute lung injury. Chest. 2010; 138: 965-72.

40. Czechowski M, Karpel E, Duda I, Grzybowska K. [Surfactant protein D as a biomarker for lung injury]. Anestezjol Intens Ter. 2008; 40: 44-8.

Received : 07 Jul 2013
Accepted : 10 Jul 2013
Published : 02 Aug 2013
Journals
Annals of Otolaryngology and Rhinology
ISSN : 2379-948X
Launched : 2014
JSM Schizophrenia
Launched : 2016
Journal of Nausea
Launched : 2020
JSM Internal Medicine
Launched : 2016
JSM Hepatitis
Launched : 2016
JSM Oro Facial Surgeries
ISSN : 2578-3211
Launched : 2016
Journal of Human Nutrition and Food Science
ISSN : 2333-6706
Launched : 2013
JSM Regenerative Medicine and Bioengineering
ISSN : 2379-0490
Launched : 2013
JSM Spine
ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Arthritis
ISSN : 2475-9155
Launched : 2016
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
Author Information X