Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2020, Vol. 11 Issue (5) : 1174-1191     DOI: 10.14336/AD.2020.0608
Review Article |
Stem Cell Based Therapy Option in COVID-19: Is It Really Promising?
Duygu Koyuncu Irmak1,2,*, Hakan Darıcı1,2,3, Erdal Karaöz1,2,3,4
1Istinye University, Faculty of Medicine, Department of Histology & Embryology, Istanbul, Turkey
2Istinye University, Stem Cell and Tissue Engineering R&D Center, Istanbul, Turkey
3Istinye University, 3D Bioprinting Design & Prototyping R&D Center, Istanbul, Turkey
4Liv Hospital, Stem Cell and Regenerative Therapies Center (LivMedCell), Istanbul, Turkey
Download: PDF(647 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    

The COVID-19 patients were first detected in China, in December 2019, then the novel virus with associated pneumonia and other diseases spread quickly to worldwide becoming a serious public health intimidation. Despite all the efforts, the pharmacological agents used for controlling or treating the disease, especially respiratory problems, have not been accomplished so far. Among various treatment options, mesenchymal stem cell-based cellular therapies are being investigated, because of their regeneration ability and multipotency along with other features like immunomodulation, antifibrosis and anti-inflammatory effects. This paper intends to analyze the current clinical trials on stem cell treatment of novel virus, searching and reviewing the available information and the International Clinical Trials Registry Platform (ICTRP) of World Health Organization (WHO). We concluded that the stem cell treatment of COVID-19 is found promising with pilot studies’ results, but still in the early development phase. There is an urgent need for large-scale investigations to confirm and validate the safety and efficacy profile of these therapies with reliable scientific evidence.

Keywords Stem cell      treatment      COVID-19      clinical      trials     
Corresponding Authors: Irmak Duygu Koyuncu   
About author:

These authors contributed equally to this work.

Just Accepted Date: 07 August 2020   Issue Date: 21 September 2020
E-mail this article
E-mail Alert
Articles by authors
Irmak Duygu Koyuncu
Darıcı Hakan
Karaöz Erdal
Cite this article:   
Irmak Duygu Koyuncu,Darıcı Hakan,Karaöz Erdal. Stem Cell Based Therapy Option in COVID-19: Is It Really Promising?[J]. Aging and disease, 2020, 11(5): 1174-1191.
URL:     OR
Figure 1.  Demonstration of the SARS-CoV impact during the general immune reaction function. (PRRs: pattern recognition receptors, TLR: Toll-like receptor, NLR: NOD)-like receptors, RLR: retinoic acid-inducible gene-I (RIG-I)-like receptors, IFN: Interferone).
Registry of Clinical trialsWeb Site
1Australian New Zealand Clinical Trials Registry (ANZCTR)
2Brazilian Clinical Trials Registry (ReBec)
3Chinese Clinical Trial Registry (ChiCTR)
4Clinical Research Information Service (CRiS), Republic of Korea
5United States National Library of Medicine
6Clinical Trials Registry - India (CTRI)
7Cuban Public Registry of Clinical Trials (RPCEC)
8EU Clinical Trials Register (EU-CTR)
9German Clinical Trials Register (DRKS)
10Iranian Registry of Clinical Trials (IRCT)
11Japan Primary Registries Network (JPRN)
12Thai Clinical Trials Registry (TCTR)
13Lebanese Clinical Trials Registry (LBCTR)
14The Netherlands National Trial Register (NTR)
15Pan African Clinical Trial Registry (PACTR)
16Peruvian Clinical Trial Registry (REPEC)
17Sri Lanka Clinical Trials Registry (SLCTR)
Table 1  Clinical trials and web sites.
Figure 1.  First step trial selection by searching in the International Clinical Trials Registry Platform (ICTRP) of WHO with COVID-19, Coronavirus, New Coronavirus, SARS-CoV-19 key words. The clinical trials are either excluded or selected based on the study type (interventional and treatment trials are selected) and study phase (only the trials whose phase of development mentioned are selected. The further selection is done by the additional key word of stem cell and finally 16 trials are selected as a result of first step trial selection. (search date: 18 April 2020)
Trial IDPublic titleRecruitment StatusInclusion age
ChiCTR2000029569Safety and efficacy of umbilical cord blood mononuclear cells conditioned medium in the treatment of severe and critically novel coronavirus pneumonia (COVID-19): a randomized controlled trialNot Recruiting18-
ChiCTR2000030138Clinical Trial for Human Mesenchymal Stem Cells in the Treatment of Severe Novel Coronavirus Pneumonia (COVID-19)Not Recruiting1675
ChiCTR2000029990Clinical trials of mesenchymal stem cells for the treatment of pneumonitis caused by novel coronavirus pneumonia (COVID-19)Recruiting1895
ChiCTR2000030300Umbilical cord mesenchymal stem cells (hucMSCs) in the treatment of high-risk novel coronavirus pneumonia (COVID-19) patientsRecruiting1875
ChiCTR2000031494Clinical study for stem cells in the treatment of severe novel coronavirus pneumonia (COVID-19)Recruiting1890
ChiCTR2000031430Clinical study of human umbilical cord mesenchymal stem cells in the treatment of novel coronavirus pneumonia (COVID-19) induced pulmonary fibrosisRecruiting1880
NCT04252118Mesenchymal Stem Cell Treatment for Pneumonia Patients Infected With COVID-19Recruiting1870
NCT04276987A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus PneumoniaNot yet Recruiting1875
NCT04313322Treatment of COVID-19 Patients Using Wharton’s Jelly-Mesenchymal Stem CellsRecruiting18-
NCT04315987NestCell® Mesenchymal Stem Cell to Treat Patients With Severe COVID-19 Pneumonia (HOPE)Not yet Recruiting18-
NCT04331613Safety and Efficacy of CAStem for Severe COVID-19 Associated With/Without ARDSRecruiting1870
NCT04339660Clinical Research of Human Mesenchymal Stem Cells in the Treatment of COVID-19 PneumoniaRecruiting1875
NCT04336254Safety and Efficacy Study of Allogeneic Human Dental Pulp Mesenchymal Stem Cells to Treat Severe COVID-19 PatientsRecruiting1865
NCT04288102Treatment With Mesenchymal Stem Cells for Severe Corona Virus Disease 2019 (COVID-19)Recruiting1875
NCT04302519Novel Coronavirus Induced Severe Pneumonia Treated by Dental Pulp Mesenchymal Stem CellsNot yet Recruiting1875
NCT04269525Umbilical Cord (UC)-Derived Mesenchymal Stem Cells (MSCs) Treatment for the 2019-novel Coronavirus (nCOV) PneumoniaRecruiting1875
Table 2  Selected trials in ICTP of WHO.
Protocol design: Selected Trials with Randomized Controlled Design
Trial IDPhase / Target participantsBlindingIntervention
ChiCTR2000029569Phase 0 /
30 subjects
Open labelExperimental group: conventional treatment combined with umbilical cord mesenchymal stem cellconditioned medium group
Control group: Conventional treatment
NCT04339660Phase 1-2 /
30 Subjects
Triple-blindedExperimental group: conventional and treatment with umbilical cord MSCs,
1x106 UC-MSCs /kg body weight suspended in 100mL saline Control group: conventional treatment and Placebo intravenously. Placebo 100mL saline intravenously
NCT04336254Phase 1-2 /
20 Subjects
Triple-blindedExperimental group: allogeneic human dental pulp stem cells
Intravenous injection of 3.0x107 human dental pulp stem cells solution (30ml) on day 1, day 4 and day 7, based on routine treatment of COVID-19 Control group: Intravenous saline injection as Placebo Intravenous injection of 3ml of 0.9% saline on day 1, day 4 and day 7, based on routine treatment of COVID-19
NCT04288102Phase 2 /
90 Subjects
Quadruple-blindedExperimental Group: Conventional treatment plus 3 times of MSCs(4.0x107 cells per time) intravenously at Day 0, Day 3, Day 6.
Control Group: Saline containing 1% Human serum albumin (solution of MSC) 3 times of placebo (intravenously at Day 0, Day 3, Day 6)Other: Intravenous saline injection (Placebo) Intravenous injection of 3ml of 0.9% saline on day 1, day 4 and day 7, based on routine treatment of COVID-19
ChiCTR2000030138Phase 2 /
60 subjects
Double BlindedExperimental group: Intravenous injection of human umbilical cord mesenchymal stem cells (UC-MSC); Note: routine treatment combination was not mentioned in the other records.
Control Group: Routine treatment + placebo
Table 3  The randomised controlled trials along with their development phases, participant size blinding status and the treatment intervention types to cure SARS-CoV infection in ICTP database of WHO.
Protocol design: Selected Trials with Parallel Controlled Design
Trial IDPhaseTotal target ParticipantsIntervention
ChiCTR2000029990Phase 1-2120 SubjectsExperimental group: mesenchymal stem cells.
Control group: saline. Note: Randomly divided into group A as placebo group and group B as stem cell treatment group
ChiCTR2000031494Phase 136 SubjectsExperimental group: Conventional medication + Infusion of mesenchymal stem cells;
Control group: Conventional medication.
ChiCTR2000031430Phase 2200 SubjectsExperimental group: Conventional treatment regimen + MSC treatment;
Control group: Conventional treatment regimen.
Table 4  The Parallel Controlled Design along with their development phases, participant size blinding status and the treatment intervention types to cure SARS-CoV infection in ICTP database of WHO.
Protocol design: Selected Trials with Other Design Characteristics
Trial IDPhase / Target ParticipantsDesignIntervention
NCT04252118Phase 1 /
20 Subjects
parallel open labelExperimental Group: 3 times of MSCs (3.0*10E7 MSCs intravenously at Day 0, Day 3, Day 6).
Control Group: Without MSCs Therapy but conventional treatment should be received.
NCT04276987Phase 1 /
30 Subjects
Single armMSCs-derived exosomes
(5 times aerosol inhalation of MSCs-derived exosomes (2.0*10E8 nano vesicles/3 ml at Day 1, Day 2, Day 3, Day 4, Day 5).)
NCT04313322Phase 1 /
5 Subjects
Single arm
open label
WJ-MSCs will be derived from cord tissue of newborns, screened for HIV1/2, HBV, HCV, CMV, Mycoplasma, and cultured to enrich for MSCs.
NCT04315987Phase 1 /
66 Subjects
single arm
open label
NestCell® is a mesenchymal stem cell therapy produced by Cellavita
NCT04331613Phase 1-2 /
9 Subjects
single arm
open label
CAStem will be administered intravenously.
Human Embryonic Stem Cells Derived M Cells (CAStem) A dose-escalation with 3 cohorts with 3 patients/cohort who receive doses of 3, 5 or 10 million cells/kg. If there are no safety concerns for each cohort, the dose will be escalated from lower dose to next higher dose.
NCT04302519Phase early 1 /
24 Subjects
single arm
open label
Dental pulp mesenchymal stem cells
On the basis of clinical standard treatment, the injection of dental mesenchymal stem cells was increased on day 1, 3 and 7 of the trial.
Table 5  The trials with other design characteristics along with their development phases, participant size blinding status and the treatment intervention types to cure SARS-CoV infection in ICTP database of WHO.
Trial IDTherapyRouteDoseApplication intervalsCondition
ChiCTR2000029569Conventional treatment (CT) combined with UC-MSC conditioned mediumNot mentionedNot mentionedNot MentionedSevere or/to critical pneumonia diagnosis due to SARS-CoV infection
ChiCTR2000030138CT + UC-MSC
CT + placebo
IV injectionNot mentionedNot MentionedSevere Novel Coronavirus Pneumonia
ChiCTR2000029990MSCs or salineNot mentionedNot mentionedNot MentionedModerate to severe cases of new coronavirus pneumonia
ChiCTR2000030300 (Cancelled)(UC-MSCs)Not mentionedNot mentionedNot MentionedPatients with high risk
ChiCTR2000031494CT or CT plus UC-MSCsIVNot mentionedNot MentionedSevere novel coronavirus pneumonia
ChiCTR2000031430CT + UC-MSCsIV4*107 cells/applicationon days 0, 3, and 6 for a total of 3 timesNovel Coronavirus Pneumonia (COVID-19) severity not mentioned
NCT04252118CT plus MSCsIV1*107cells/applicationat Day 0, Day 3, Day 6).Pneumonia Patients Infected With COVID-19 severity not mentioned
NCT04276987CT plus MSCs-derived exosomesaerosol inhalation1*108 nano vesicles/3 mlat Day 1, Day 2, Day 3, Day 4, Day 5Severe or/to critical pneumonia diagnosis due to SARS-CoV infection
NCT04313322WJ-MSCsIV1*106 cells/kgThe three doses will be 3 days apart form each other. 3 weeks follow upCOVID-19 (ever, respiratory destress, pneumonia, cough, sneezing, diarrhea) severity not mentioned
NCT04313322WJ-MSCsIV1*10e6 cells/kgThe three doses will be 3 days apart form each other.COVID-19 (ever, respiratory destress, pneumonia, cough, sneezing, diarrhea) severity not mentioned.
NCT04315987CT plus MSCsIV2*107cells/applicationon days 1, 3 and 5 and if necessary on day 7Severe COVID-19 pneumonia.
NCT04331613CAStem, immunity- and matrix-regulatory cells (IMRCs), differentiated from hESCsIV3/5/10*106 cells/kg. Escalating doses.intervals not mentioned3 cohorts with 3 patients/cohort with severe COVID-19 associated w/wo ARDS.
NCT04339660CT plus MSCsIV1*106 cells/kg1 time, or with an interval of 1 weekCritically ill COVID-19 pneumonia
NCT04336254CT plus hDP-MSCsIV3*107cells/bag * 3 bagsinjection of on day 1, day 4 and day 7Severe pneumonia caused by COVID-19
NCT04288102CT plus MSCsIV4.0*107at Day 0, Day 3, Day 6.COVID-19 Patients with Severe Convalescence
NCT04302519CT plus hDP-MSCsIV1.0x106 cells /kg.on day 1, 3 and 7 of the trial.Novel Coronavirus Induced Severe Pneumonia
NCT04269525UC-MSCsIV3.3*107/50ml bags*3bag,on day 1, day 3, day 5, and day 7.Serious Pneumonia and Critical Pneumonia Caused by the 2019-nCOV Infection
Table 6  The MSC treatment doses, route of administration, treatment/ application intervals and target lung condition’s name and grade (mild, moderate, severe or critical).
PROSComments on PROSCONSComments on CONS
AccessibilityThey are easily accessible and can be isolated from various tissuesCell SourcingThe cell-based therapies need the cells need to be expanded in large quantities while protecting their uniformity in activity and staying pathogen free. The use of human embryonic stem (ES) cells versus adult SCs is still a matter of debate. The current political decision makers strongly favoring adult stem cell option.
PotencyThey are multipotent stem cellsPlasticityAdult SCs have certain plasticity to transdifferentiate from one lineage pathway to another. Besides, instead of transdifferentiating with normal diploid chromosomal numbers, SCs may fuse with tissue-specific differentiated cells causing polyploidy. MSCs differentiation was reported to lead to tissue ossification or calcification in animal models which is also a potential risk in human use.
VolumeMSCs can easily expand to clinical volume in a suitable period of timeSafety Concerns of using transformed cellsIn children with adenosine deaminase deficiency, the autologous transplantation of genetically modified hematopoietic stem cells was reported to lead to severe immunodeficiency followed by acute leukemia in some of the patients. Nerve cells implantation in Parkinson’s disease patients was reported the high rate of severe and uncontrollable dyskinetic activity as adverse effect. Also, myoblast implantation into the heart tissue showed adverse event of increased rates of cardiac arrhythmias.
StorageMSCs can be stored for repetitive therapeutic usageChoosing autologous or non-autologous human cellsRegardless of the chosen method, each treatment has important regulatory and practical difficulties, and logistics of delivery can be another issue, i.e. to maintain the uniformity of cells, to avoid any contamination during cell processing.
No Reported Safety issuesClinical trials of MSCs so far haven’t shown adverse reactions to allogeneic MSC.Maintenance of cell viabilityThe nutrient and oxygen delivery to the cellular implant is of vital importance for viability of the cells. It has been still in experimental stage to use the neovascular capillary bed in and around the cell implant and intravascular cell encapsulation implant approach not having use in human in clinics.
EffectivenessEffectiveness of MSCs have been obviously documented in several clinical trials*The references used to compile the information for this table: 22, 33, 77, 78, 79, 80, 81.
Table 7  The Pros and Cons of MSCs use for treatment purposes in general*.
[1] Velavan TP, Meyer CG (2020). The COVID-19 epidemic. Trop Med Int Health. 25:278-280.
[2] Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. (2020). Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med, 382:1708-1720.
[3] Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 395(10223):497-506.
[4] Zhou Y, Yamamoto Y, Xiao Z, Ochiya T (2019). The Immunomodulatory Functions of Mesenchymal Stromal/Stem Cells Mediated via Paracrine Activity. J Clin Med, 8: 1025.
[5] Demircan PC, Sariboyacı AE, Unal ZS, Gacar G, Subasi C, Karaoz E (2011). Immunoregulatory effects of human dental pulp-derived stem cells on T cells: comparison of transwell co-culture and mixed lymphocyte reaction systems. Cytotherapy, 13:1205-20.
[6] Yilmaz S, Inandiklioglu N, Yildizdas D, Subasi C, Acikalin Aet al. (2013). Mesenchymal Stem Cell: Does it Work in an Experimental Model with Acute Respiratory Distress Syndrome? Stem Cell Rev and Rep 9:80-92.
[7] Ye Y, PhilipNP LagnitonSY, Enqin L, Ren-He X (2020). COVID-19: What has been learned and to be learned about the novel coronavirus disease. Int J Biol Sci, 16(10):1753-66.
[8] de Wilde AH, Snijder EJ, Kikkert M, van Hemert MJ (2018). Host Factors in Coronavirus Replication. Curr Top Microbiol Immunol, 419: 1-42.
[9] Yan-Rong G, Qing-Dong C, Zhong-Si H, Yuan-Yang T, Shou-Deng C, et al. (2020). The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status, Military Medical Research, 7:11.
[10] Singhal T (2020). A Review of Coronavirus Disease-2019 (COVID-19) The Indian Journal of Pediatrics, 87(4):281-286.
[11] Raj VS, Mou H, Smits SL, Dekkers DH, Muller MA, Dijkman R, et al. (2013). Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature, 495: 251-4.
[12] Sevajol M, Subissi L, Decroly E, Canard B, Imbert I (2014). Insights into RNA synthesis, capping, and proofreading mechanisms of SARS-coronavirus. Virus Res, 194: 90-9.
[13] Dong N, Yang X, Ye L, Chen K, Chan EW-C, Yang M, et al. (2020). Genomic and protein structure modelling analysis depicts the origin and infectivity of 2019-nCoV, a new coronavirus which caused a pneumonia outbreak in Wuhan, China. bioRxiv, preprint.
[14] Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. (2020). Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet, 395: 563-74.
[15] Ji W, Wang W, Zhao X, Zai J, Li X (2020). Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross-species transmission from snake to human. J Med Virol, 92-4.
[16] Atluri S, Manchikanti L, Hirsch JA (2020). Expanded Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) as a Therapeutic Strategy In Managing Critically Ill COVID-19 Patients: The Case for Compassionate Use. Pain Physician, 23:71-83.
[17] Hamming I, Timens W, Bulthuis ML, et al. (2004). Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus: A first step in understanding SARS pathogenesis. J Pathol, 203:631-37.
[18] Vergano M, Bertolini G, Giannini A, Gristina G, Livigni S, Mistraletti G, Petrini F (2020). Clinical ethics recommendations for admission to intensive treatments and for their suspension, in exceptional conditions of imbalance between needs and available resources. SIAARTI Press Release, 1: 58.
[19] Leng Z, Zhu R, Hou W (2020). Transplantation of ACE2 Mesenchymal stem cells improves the outcomes of patients with COVID-19 pneumonia. Aging Dis, 11:216-228.
[20] Huang C, Wang Y, Li X, et al. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 395:497-506.
[21] D’Elia RV, Harrison K, Oyston PC, Lukaszewski RA, Clark GC (2013). Targeting the “Cytokine Storm” for Therapeutic Benefit. Clin Vaccine Immunol, 20(3):319-27.
[22] Golchin A, Seyedjafari E, Ardeshirylajimi A (2020). Mesenchymal Stem Cell Therapy for COVID-19: Present or Future. Stem Cell Rev Rep, 13: 1-7. Epub ahead of print.
[23] Mehta P, Mcauley DF, Brown M, Sanchez E, Tattersall RS, Manson J, et al. (2020). Correspondence COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet, 6736(20) 19-20.
[24] Ben Addi A, Lefort A, Hua X, Libert F, Communi D, Ledent C, et al. (2008). Modulation of murine dendritic cell function by adenine nucleotides and adenosine: involvement of the A(2B) receptor. European Journal of Immunology, 38: 1610-20.
[25] Lu X, Pan J, Tao J, Guo D (2011). SARS-CoV nucleocapsid protein antagonizes IFN-beta response by targeting initial step of IFN-beta induction pathway, and its C-terminal region is critical for the antagonism. Virus Genes, 42: 37-45.
[26] Channappanavar R, Perlman S (2017). Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Seminars in Immunopathology, 39: 529-39.
[27] Petit-Zeman S (2001). Regenerative medicine. Nat Biotechnol, 19:201-206.
[28] Humes HD (2005). Stem cells: the next therapeutic frontier. Transactions of the American Clinical and Climatological Association, 116: 167-184.
[29] Bianco P, Robey PG (2001). Stem cells in tissue engineering. Nature, 414:118-21.
[30] Freed CR, Greene PE, Breeze RE, Tsai WY, Du Mouchel W, Kao R, et al. (2001). Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med, 344(10):710-9.
[31] Hage`ge AA, Carrion C, Menasche P, Vilquin JT, Duboc D, Marolleau JP, et al. (2003). Viability and differentiation of autologous skeletal myoblast grafts in ischaemic cardiomyopathy. Lancet, 361:491-92.
[32] Watanabe FD, Mullon CJ, Hewitt WR, Arkadopoulos N, Kahaku E, Eguchi S, et al. (1997). Clinical experience with a bioartificial liver in the treatment of severe liver failure. A phase I clinical trial. Ann Surg, 225:484-91.
[33] Humes HD, Weitzel WF, Bartlett RH, Swaniker FC, Paganini EP (2003). Renal cell therapy is associated with dynamic and individualized responses in patients with acute renal failure. Blood Purif, 21:64-7.
[34] Behnke J, Kremer S, Shahzad T, et al. (2020). MSC-based therapies-new perspectives for the injured lung. J Clin Med, 3:9.
[35] Li D, Liu Q, Qi L, Dai X, Liu H, Wang Y (2016). Low levels of TGF-β1 enhance human umbilical cord-derived mesenchymal stem cell fibronectin production and extend survival time in a rat model of lipopolysaccharide-induced acute lung injury. Mol Med Rep, 14:1681-1692.
[36] Iyer SS, Co C, Rojas M (2009). Mesenchymal stem cells and inflammatory lung diseases. Panminerva Med, 51:5-16.
[37] Manchikanti L, Centeno CJ, Atluri S, et al. (2020). Bone marrow concentrate (BMC) therapy in musculoskeletal disorders: Evidence-based policy position statement of American Society of Interventional Pain Physicians (ASIPP). Pain Physician, 23: 83-129.
[38] Chen J, Hu C, Chen L, Tang L, Zhu Y, Xu X, Chen L, Gao H, Lu X, Yu L et al. (2020). Clinical study of mesenchymal stem cell treating acute respiratory distress syndrome induced by epidemic Influenza A (H7N9) infection, a hint for COVID-19 treatment. Engineering, 10: 1016.
[39] Khoury M, Alcayaga MF, Illanes SE, Figueroa FE (2014). The promising potential of menstrual stem cells for antenatal diagnosis and cell therapy. Front Immunol, 5:205.
[40] Chen L, Qu J, Cheng T, Chen X, Xiang C (2019). Menstrual blood-derived stem cells: toward therapeutic mechanisms, novel strategies, and future perspectives in the treatment of diseases. Stem Cell Res Ther, 10:406.
[41] Chen L, Qu J, Xiang C (2019). The multi-functional roles of menstrual blood-derived stem cells in regenerative medicine. Stem Cell Res Ther, 10(1):1-10.
[42] GolchinA, FarahanyT, KhojastehA, SoleimanifarF, ArdeshirylajimiA (2018). The clinical trials of Mesenchymal stem cell therapy in skin diseases: An update and concise review. Curr Stem Cell Res Ther, 14(1) 22-33.
[43] Yu B, Zhang X, Li X (2014). Exosomes derived from mesenchymal stem cells. Int J Mol Sci, 15: 4142-57.
[44] Zhang B, Shen L, Shi H, Pan Z, WuL, Yan Y, et al. (2016). Exosomes from Human Umbilical Cord Mesenchymal Stem Cells: Identification, Purification, and Biological Characteristics. Stem Cells International, 1929536: 1-11.
[45] Sun L, Xu R, Sun X, Quian Y, Han Y, Zhu W, et al. (2016). Safety evaluation of exosomes derived from human umbilical cord mesenchymal stromal cell, Cytotherapy, 18: 413-422.
[46] Gatti S, Bruno S, Deregibus MC, Sordi A, Cantaluppi V, Tetta C, et al. (2011). Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. Nephrol Dial Transplant, 26:1474-1483.
[47] Zhou Y, Xu H, Xu W, Wang B, Wu H, Tao Y, et al. (2013). Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro. Stem Cell Res Ther, 4:34.
[48] Rahmani B, Tielsch J, Katz J, Gottsch J, et al. (1996). The cause-specific prevalence of visual impairment in an urban population. The Baltimore eye survey. Ophthalmology, 103: 1721-1726.
[49] Kelly NE, Wendel RT (1991). Vitreous surgery for idiopathic macular holes: Results of a pilot study, Arch. Ophthalmol, 109:654-659.
[50] Iwata N, Higuchi M, Saido TC (2005). Metabolism of amyloid-beta peptide and Alzheimer’s disease. Pharmacol, 108:129-148.
[51] Krause DL, Muller N (2010). Neuroin?ammation, microglia and implications for antiin?ammatory treatment in Alzheimer’s disease, Int J Alzheimers Dis, 732806:1-9.
[52] Brown GC (2007). Mechanisms of in?ammatory neurodegeneration: iNOS and NADPH oxidase, Biochem. Soc Trans, 35: 1119-1121.
[53] Bellora F, Castriconi R, Dondero A, Reggiardo G, Moretta L, Mantovani A, et al. (2010). The interaction of human natural killer cells with either unpolarized or polarized macrophages results in different functional outcomes, Proc Natl Acad Sci, 107: 21659-21664.
[54] Hare JM, Traverse JH, Henry TD, Dib N, Strumpf RK, Schulman SP, et al. (2009). A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction, J Am Coll Cardiol, 54: 2277-2286.
[55] Vassalli G, Moccetti T (2011). Cardiac repair with allogeneic mesenchymal stem cells after myocardial infarction. Swiss Med Wkly, 141: 13209.
[56] Golchin A, Farahany TZ (2019). Biological products: Cellular therapy and FDA approved products. Stem Cell Reviews and Reports, 15(2): 1-10.
[57] Williams R (2020). Are Mesenchymal Stem Cells a Promising Treatment for COVID-19? The Scentst Magazine, 19-67402.
[58] Wood C (2020). First cell treatment to fight the coronavirus awaits FDA approval for clinical trial. CNBC Broadcast, 3-31.
[59] Ji F, Li Y, Li Z, Jin Y, Liu W (2019). Stem cells as a potential treatment for critically ill patients with coronavirus disease. Stem Cells Transl Med, 1-2.
[60] Huang C, Wang Y, Li X, et al. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan China. Lancet, 395:497-506.
[61] Xie L, Liu Y, Fan B, et al. (2005). Dynamic changes of serum SARS-coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge. Respir Res, 6:5.
[62] Russell B, Moss C, George1 G, Santaolalla A, Cope A, Papa S, Van Hemelrijck M (2020). Associations between immune-suppressive and stimulating drugs and novel COVID-19—a systematic review of current evidence. ECancer, 14:1022.
[63] Connick P, Kolappan M, Crawley C, Webber DJ, Patani R, Michell AW, et al. (2012). Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurology, 11:150156.
[64] Wilson JG, Liu KD, Zhuo NJ, Caballero L, McMillan M, Fang XH, et al. (2015). Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respiratory Medicine, 3:24-32.
[65] Hashmi S, Ahmed M, Murad MH, Litzow MR, Adams RH, Ball LM, et al. (2016). Survival after mesenchymal stromal cell therapy in steroid refractory acute graft-versus-host disease: systematic review and meta-analysis. Lancet Haematology, 3: 45-52.
[66] Kamen DL, Nietert PJ, Wang H, Duke T, Cloud C, Robinson A, et al. (2018). Safety and efficacy of allogeneic umbilical cord-derived mesenchymal stem cells (MSCs) in patients with SLE: results of an open-label phase I study. Lupus, 5(Suppl 2):1-81.
[67] Shetty AK (2020). Mesenchymal Stem Cell Infusion Shows Promise for Combating Coronavirus (COVID-19)- Induced Pneumonia. Aging Dis, 11(2): 462-464.
[68] Ozdemir AT, Ozdemir RB, Kirmaz C, Sarıboyaci AE, Halbutog, llarıeZSU, Ozel C, Karaoz E (2016). The paracrine immunomodulatory interactions between the human dental pulp derived mesenchymal stem cells and CD4 T cell subsets. Cellular Immunology, 310: 108-15.
[69] Kong D, Liu X, Li X, Hu J, Li X, Xiao J (2019). Mesenchymal stem cells significantly improved treatment effects of Linezolid on severe pneumonia in a rabbit model. Bioscience Reports, 39(2455): 1-15.
[70] Marshall G (1948). Streptomycin treatment of pulmonary tuberculosis—a medical research council investigation. British Medical Journal, 2: 769-82.
[71] Bondemark L, Ruf S (2015). Randomized controlled trial: the gold standard or an unobtainable fallacy? European Journal of Orthodontics, 37(5): 457-61.
[72] Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q (2020). Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging Dis, 11(2): 216-28.
[73] Yang N, Shen HM (2020). Targeting the Endocytic Pathway and Autophagy Process as a Novel Therapeutic Strategy in COVID-19. Int J Biol Sci, 16:1774-31.
[74] Zhao RC (2020). Stem Cell-Based Therapy for Coronavirus Disease 2019. Stem Cells and Development, 29(11): 679-81.
[75] Matthay MA, Calfee CS, Zhuo H, Thompson BT, Wilson JG, Levitt JE, et al. (2019). Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial. Lancet Respir Med, 7(2):154-62.
[76] Simonson OE, Mougiakakos D, Heldring N, Bassi G, Johansson HJ, Dalen M, et al. (2015). In vivo effects of mesenchymal stromal cells in two patients with severe acute respiratory distress syndrome. Stem Cells Transl Med, 4(10):1199-213.
[77] Sun J, He WT, Wang L, Lai A, Ji X, Zhai X, et al. (2020). COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives. Trends Mol Med, 26(5): 483-495.
[78] Lupia T, Scabini S, Pinna SM, Di Perri G, De Rosa FG, Corcione S (2020). 2019-novel Coronavirus Outbreak: A New Challenge. Journal of Global Antimicrobial Resistance, 21:22-27.
[79] Wang LS, Wang YR, Ye DW, Liu QQ (2020). A review of the 2019 Novel Coronavirus (COVID-19) based on current evidence. Int J Antimicrob Agents, 12:43.
[80] Zhang B, Zhang J, Chen H, Yang K, Zhang S (2020). Unmatched clinical presentation and chest CT manifestation in a patient with severe coronavirus disease 2019 (COVID-19). Quant Imaging Med Surg, 10(4):871-873.
[81] Zheng Z, Peng F, Xu B, Zhao J, Liu H, Peng Jet al. (2020). Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis. The British Infection Association. J Infect, 15:12.
[1] Pietro Gentile,Aris Sterodimas,Jacopo Pizzicannella,Claudio Calabrese,Simone Garcovich. Research progress on Mesenchymal Stem Cells (MSCs), Adipose-Derived Mesenchymal Stem Cells (AD-MSCs), Drugs, and Vaccines in Inhibiting COVID-19 Disease[J]. Aging and disease, 2020, 11(5): 1191-1201.
[2] Undurti N Das. Bioactive Lipids as Mediators of the Beneficial Action(s) of Mesenchymal Stem Cells in COVID-19[J]. Aging and disease, 2020, 11(4): 746-755.
[3] Ting Wu,Zhihong Zuo,Shuntong Kang,Liping Jiang,Xuan Luo,Zanxian Xia,Jing Liu,Xiaojuan Xiao,Mao Ye,Meichun Deng. Multi-organ Dysfunction in Patients with COVID-19: A Systematic Review and Meta-analysis[J]. Aging and disease, 2020, 11(4): 874-894.
[4] Pedro C Lara,David Macías-Verde,Javier Burgos-Burgos. Age-induced NLRP3 Inflammasome Over-activation Increases Lethality of SARS-CoV-2 Pneumonia in Elderly Patients[J]. Aging and disease, 2020, 11(4): 756-762.
[5] Michael D Schwartz,Stephen G Emerson,Jennifer Punt,Willow D Goff. Decreased Naïve T-cell Production Leading to Cytokine Storm as Cause of Increased COVID-19 Severity with Comorbidities[J]. Aging and disease, 2020, 11(4): 742-745.
[6] Hasim Eray Copcu. Potential Using of Fat-derived Stromal Cells in the Treatment of Active Disease, and also, in Both Pre- and Post-Periods in COVID-19[J]. Aging and disease, 2020, 11(4): 730-736.
[7] Feng He, Yibo Quan, Ming Lei, Riguang Liu, Shuguang Qin, Jun Zeng, Ziwen Zhao, Na Yu, Liuping Yang, Jie Cao. Clinical features and risk factors for ICU admission in COVID-19 patients with cardiovascular diseases[J]. Aging and disease, 2020, 11(4): 763-769.
[8] Agnieszka Neumann-Podczaska,Salwan R Al-Saad,Lukasz M Karbowski,Michal Chojnicki,Slawomir Tobis,Katarzyna Wieczorowska-Tobis. COVID 19 - Clinical Picture in the Elderly Population: A Qualitative Systematic Review[J]. Aging and disease, 2020, 11(4): 988-1008.
[9] Nir Barzilai, James C Appleby, Steven N Austad, Ana Maria Cuervo, Matt Kaeberlein, Christian Gonzalez-Billault, Stephanie Lederman, Ilia Stambler, Felipe Sierra. Geroscience in the Age of COVID-19[J]. Aging and disease, 2020, 11(4): 725-729.
[10] Peter A LeWitt, Steve Kymes, Robert A Hauser. Parkinson Disease and Orthostatic Hypotension in the Elderly: Recognition and Management of Risk Factors for Falls[J]. Aging and disease, 2020, 11(3): 679-691.
[11] Giuseppe Colloca, Luca Tagliaferri, Beatrice Di Capua, Maria Antonietta Gambacorta, Vito Lanzotti, Andrea Bellieni, Silvio Monfardini, Lodovico Balducci, Roberto Bernabei, William C Cho, Vincenzo Valentini. Management of The Elderly Cancer Patients Complexity: The Radiation Oncology Potential[J]. Aging and disease, 2020, 11(3): 649-657.
[12] Xiaotian Dong, Mengyan Wang, Shuangchun Liu, Jiaqi Zhu, Yanping Xu, Hongcui Cao, Lanjuan Li. Immune Characteristics of Patients with Coronavirus Disease 2019 (COVID-19)[J]. Aging and disease, 2020, 11(3): 642-648.
[13] Sankha Shubhra Chakrabarti, Upinder Kaur, Anindita Banerjee, Upasana Ganguly, Tuhina Banerjee, Sarama Saha, Gaurav Parashar, Suvarna Prasad, Suddhachitta Chakrabarti, Amit Mittal, Bimal Kumar Agrawal, Ravindra Kumar Rawal, Robert Chunhua Zhao, Indrajeet Singh Gambhir, Rahul Khanna, Ashok K Shetty, Kunlin Jin, Sasanka Chakrabarti. COVID-19 in India: Are Biological and Environmental Factors Helping to Stem the Incidence and Severity?[J]. Aging and disease, 2020, 11(3): 480-488.
[14] Selçuk Öztürk, Ayşe Eser Elçin, Yaşar Murat Elçin. Mesenchymal Stem Cells for Coronavirus (COVID-19)-Induced Pneumonia: Revisiting the Paracrine Hypothesis with New Hopes?[J]. Aging and disease, 2020, 11(3): 477-479.
[15] Pietro Gentile, Aris Sterodimas. Adipose Stem Cells (ASCs) and Stromal Vascular Fraction (SVF) as a Potential Therapy in Combating (COVID-19)-Disease[J]. Aging and disease, 2020, 11(3): 465-469.
Full text



Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail:
Powered by Beijing Magtech Co. Ltd