249:
transplantation site. Early cell passages have been shown to be more efficient paracrine activity than later passages. The delivered cells (via local or systemic administration) remain viable for a relatively short period (days-weeks) and then die. This includes cells that naturally secrete the relevant therapeutic factors, or which undergo epigenetic changes or genetic engineering that causes the cells to release large quantities of a specific molecule. Examples of this include cells that secrete factors which facilitate angiogenesis, anti-inflammation, and anti-apoptosis. This mode of action is proposed by companies such as
166:. Annually an estimated 18,000 patients require potentially life-saving bone marrow transplants in the US. For a long time, bone marrow transplantation was the only clinically applicable method of cell transplantation, however, since the 1990s, cell therapy has been investigated for a wide scale of pathologies and disorders. Cell therapy provided a novel approach to effectuate therapeutic efficacy. Previously, medical agents could only be effective by directing and inducing the patients own cells. However, in many diseases and disorders, cell are compromised by
581:. Cell and gene therapies require manufacturer and distributors alike to implement new systems and processes in order to ensure safe handling and delivery. Additionally, on-demand inventory therefore becomes more and more important, especially with regard to unforeseeable events like the COVID-19 pandemic, so that supply chain interruptions can be prevented. Furthermore recent changes as a result of the COVID 19 pandemic and political instability in Europe, secondary to Brexit, have further impacted the logistics chain for cellular therapies.
104:
95:
prevent the human body rejecting transplanted organs, leading in time to successful bone marrow transplantation as has become common practice in treatment for patients that have compromised bone marrow after disease, infection, radiation or chemotherapy. In recent decades, however, stem cell and cell transplantation has gained significant interest by researchers as a potential new therapeutic strategy for a wide range of diseases, in particular for degenerative and immunogenic pathologies.
355:. Nevertheless, an autologous strategy is often costly due to patient-by-patient processing, thus preventing the option to create large quality-controlled batches. Moreover, autologous strategies generally do not allow for product quality and effectiveness testing prior to transplantation, as it is highly donor (thus patient) dependent. This is a particular concern as often the patient functioning as donor is diseased, and this can impact cell potency and quality.
48:
181:, or simply a reduction in the number of cells. Cell therapy offers a new strategy that supports the introduction of new and active cells to restore previously compromised or deteriorated tissue- and organ structures. As such, in recent times, cell therapy has been recognized as an important field in the treatment of human disease, and investigations are ongoing in
482:
grafting was first published in 1957, there have been significant advancements in HSCs therapy. Following that, syngeneic marrow infusion and allogeneic marrow grafting were performed successfully. HSCs therapy can also render its cure by reconstituting damaged blood-forming cells and restoring the immune system after high-dose chemotherapy to eliminate disease.
467:(MI) resulted in significant reduction of damaged regions and improvement in heart function. Clinical trials for treatment of acute MI with Prochymal by Osiris Therapeutics are underway. Also, a clinical trial revealed huge improvements in nerve conduction velocities in Hurler's Syndrome patients infused with BM MSCs from HLA-identical siblings.
460:(HLA)-identical siblings to patients with OI. Results show that MSCs can develop into normal osteoblasts, leading to fast bone development and reduced fracture frequencies. A more recent clinical trial showed that allogeneic fetal MSCs transplanted in utero in patients with severe OI can engraft and differentiate into bone in a human fetus.
493:
In addition to bone marrow-derived HSCs, the use of alternative sources such as umbilical cord blood (UCB) and peripheral blood stem cells (PBSCs) has been increasing. In comparison with bone marrow-derived HSC recipients, PBSC recipients who had myeloid malignancies reported a faster engraftment and
481:
Hematopoietic stem cells (HSCs), derived from bone marrow or blood, are cells with the abilities to self-renew and to differentiate into all types of blood cells, especially those involved in the human immune system. Thus, they can be used to treat blood and immune disorders. Since human bone marrow
217:
Stem, progenitor, or mature cell engraftment, differentiation, and long-term replacement of damaged tissue. In this paradigm multipotent or unipotent cells differentiate into a specific cell type in the lab or after reaching the site of injury (via local or systemic administration). These cells then
485:
There are three types of HSC transplantation: syngeneic, autologous, and allogeneic transplants. Syngeneic transplantations occur between identical twins. Autologous transplantations use the HSCs obtained directly from the patient and hence avoid complications of tissue incompatibility; whereas
94:
Cell therapy originated in the nineteenth century when scientists experimented by injecting animal material in an attempt to prevent and treat illness. Although such attempts produced no positive benefit, further research found in the mid twentieth century that human cells could be used to help
369:
In xenogeneic cell therapies, the recipient will receive cells from another species. For example, the transplantation of pig derived cells to humans. Currently, xenogeneic cell therapies primarily involve human cell transplantation into experimental animal models for assessment of efficacy and
212:
Cell therapy is targeted at many clinical indications in multiple organs and by several modes of cell delivery. Accordingly, the specific mechanisms of action involved in the therapies are wide-ranging. However, there are two main principles by which cells facilitate therapeutic action:
248:
Cells that have the capacity to release soluble factors such as cytokines, chemokines, and growth factors which act in a paracrine or endocrine manner. These factors facilitate self-healing of the organ or region by inducing local (stem) cells or attracting cells to migrate towards the
123:(1882–1971) – who has been called the inventor of cell therapy – attempted to cure a patient by injecting material from calf embryos. Niehans claimed to have treated many people for cancer using this technique, though his claims have never been validated by research.
51:
Adoptive T-cell therapy. Cancer specific T-cells can be obtained by fragmentation and isolation of tumour infiltrating lymphocytes, or by genetically engineering cells from peripheral blood. The cells are activated and grown prior to transfusion into the recipient (tumour
126:
In 1953 researchers found that laboratory animals could be helped not to reject organ transplants by pre-inoculating them with cells from donor animals; in 1968, in
Minnesota, the first successful human bone marrow transplantation took place. In more recent work,
444:
MSCs are immunomodulatory, multipotent and fast proliferating and these unique capabilities mean they can be used for a wide range of treatments including immune-modulatory therapy, bone and cartilage regeneration, myocardium regeneration and the treatment of
548:
labels this as "senseless", since "cells from the organs of one species cannot replace the cells from the organs of other species" and because a number of serious adverse effects have been reported. Of this alternative, animal-based form of cell therapy, the
564:
A number of manufacturers are turning to automated methods of production, eliminating human involvement and risk of human error. Automated methods of cell therapy manufacturing have opened up larger scale production of higher quality products at lower cost.
281:
manufacturing, the allogenic methodology is promising because unmatched allogenic therapies can form the basis of "off the shelf" products. There is research interest in attempting to develop such products to treat conditions including
660:
2298:
Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, et al. (March 1999). "Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta".
403:
varies from country to country, with some countries banning it outright. Nevertheless, these cells are being investigated as the basis for a number of therapeutic applications, including possible treatments for
2631:
Sharma S, Gurudutta GU, Satija NK, Pati S, Afrin F, Gupta P, et al. (December 2006). "Stem cell c-KIT and HOXB4 genes: critical roles and mechanisms in self-renewal, proliferation, and differentiation".
1573:
Deuse, T., C. Peter, et al. (2009). "Hepatocyte growth factor or vascular endothelial growth factor gene transfer maximizes mesenchymal stem cell-based myocardial salvage after acute myocardial infarction."
114:
Cell therapy can be defined as therapy in which cellular material is injected or otherwise transplanted into a patient. The origins of cell therapy can perhaps be traced to the nineteenth century, when
2391:
Koç ON, Day J, Nieder M, Gerson SL, Lazarus HM, Krivit W (August 2002). "Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH)".
780:
Zhou X, Haraldsson T, Nania S, Ribet F, Palano G, Heuchel R, Löhr M, van der
Wijngaart W (2018). "Human Cell Encapsulation in Gel Microbeads with Cosynthesized Concentric Nanoporous Solid Shells".
2588:
Bhardwaj G, Murdoch B, Wu D, Baker DP, Williams KP, Chadwick K, et al. (February 2001). "Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation".
2145:
D'Amour KA, Bang AG, Eliazer S, Kelly OG, Agulnick AD, Smart NG, et al. (November 2006). "Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells".
131:
is pursued as a means to shield therapeutic cells from the host immune response. Recent work includes micro-encapsulating cells in a gel core surrounded by a solid, but permeable, shell.
486:
allogeneic transplantations involve the use of donor HSCs, either genetically related or unrelated to the recipient. To lower the risks of transplant, which include graft rejection and
561:
Despite being one of the fast growing areas within Life
Sciences, the manufacturing of cell therapy products is largely hindered by small scale batches and labour-intensive processes.
134:
Bone marrow transplants are the most common and well established cell transplantation therapies. The first recording of a successful bone marrow transplant, dates back to 1956 by dr.
506:
that only possess low or no proliferation ability. This tends to involve specialized cells able to facilitate specific function in the patients body (for example, transplantation of
668:
1735:
Prather WR, Toren A, Meiron M, Ofir R, Tschope C, Horwitz EM (2009). "The role of placental-derived adherent stromal cell (PLX-PAD) in the treatment of critical limb ischemia".
331:
repair. It could also involve the isolation of matured cells from diseased tissues, to be later re-implanted at the same or neighboring tissues; a strategy being assessed in
2862:
218:
integrate into the site of injury, replacing damaged tissue, and thus facilitate improved function of the organ or tissue. An example of this is the use of cells to replace
422:
Neural stem cells (NSCs) are the subject of ongoing research for possible therapeutic applications, for example for treating a number of neurological disorders such as
201:, etc. As a consequence cell therapy as a strategy has been attracting significant investments by commercial entities which suggest strong prospects for future growth.
553:
say: "Available scientific evidence does not support claims that cell therapy is effective in treating cancer or any other disease. It may in fact be lethal ...".
154:(AML), bone marrow derived cells can be infused into the patients blood stream. Here the injected cells are able to home into the affected bone marrow, integrate,
494:
better overall survival. The use of UCB requires less stringent HLA loci matching, although the time of engraftment is longer and graft failure rate is higher.
825:
463:
Besides bone and cartilage regeneration, cardiomyocyte regeneration with autologous BM MSCs has also been reported recently. Introduction of BM MSCs following
1863:
Mays RW, van't Hof W, Ting AE, Perry R, Deans R (February 2007). "Development of adult pluripotent stem cell therapies for ischemic injury and disease".
630:
253:
and
Pervasis that use adherent stromal cells or mature endothelial cells to treat peripheral artery disease and arteriovenous access complications.
1428:"Transplantation of allogenic nucleus pulposus cells attenuates intervertebral disc degeneration by inhibiting apoptosis and increasing migration"
625:
476:
573:
Logistics departments of biopharma companies experience new obstacles because of the introduction of new cell and gene therapy products, such as
204:
In 2021 Atara biotherapeutics became the first ever allogeneic T cell therapy company to be reviewed by any regulatory agency in the world (EMA)
71:
in which viable cells are injected, grafted or implanted into a patient in order to effectuate a medicinal effect, for example, by transplanting
2834:
1957:"Long-term effectiveness of local BM-MSCs for skeletal muscle regeneration: a proof of concept obtained on a pig model of severe radiation burn"
1190:
Mason C, Brindley DA, Culme-Seymour EJ, Davie NL (May 2011). "Cell therapy industry: billion dollar global business with unlimited potential".
539:
490:(GVHD), allogeneic HSCT must satisfy compatibility at the HLA loci (i.e. genetic matching to reduce the immunogenicity of the transplant).
2008:"Intervertebral disc repair with activated nucleus pulposus cell transplantation: a three-year, prospective clinical study of its safety"
544:
In alternative medicine, cell therapy is defined as the injection of non-human cellular animal material in an attempt to treat illness.
116:
107:
1818:
Newman RE, Yoo D, LeRoux MA, Danilkovitch-Miagkova A (June 2009). "Treatment of inflammatory diseases with mesenchymal stem cells".
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Van Den Berg DJ, Sharma AK, Bruno E, Hoffman R (November 1998). "Role of members of the Wnt gene family in human hematopoiesis".
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1379:"Discogenic cell transplantation directly from a cryopreserved state in an induced intervertebral disc degeneration canine model"
574:
1908:"Cartilage Repair With Autologous Bone Marrow Mesenchymal Stem Cell Transplantation: Review of Preclinical and Clinical Studies"
578:
1276:"Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction"
1793:
1688:"Delivery site of perivascular endothelial cell matrices determines control of stenosis in a porcine femoral stent model"
1590:"TNF receptor 2, not TNF receptor 1, enhances mesenchymal stem cell-mediated cardiac protection following acute ischemia"
833:
1794:"Cell Therapy Bioprocessing: Integrating Process and Product Development for the Next Generation of Biotherapeutics"
1535:"Long-term complications, immunologic effects, and role of passage for outcome in mesenchymal stromal cell therapy"
511:
487:
400:
242:
503:
2233:"Neural stem/progenitor cells as a promising candidate for regenerative therapy of the central nervous system"
103:
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151:
80:
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396:
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88:
1149:
Brindley DA, Reeve BC, Sahlman WA, Bonfiglio GA, Davie NL, Culme-Seymour EJ, Mason C (November 2011).
2946:
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or adjacent disc disease. The benefit of an autologous strategy is that there is limited concern for
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Alternative to stem- or progenitor cells, investigations are exploring the transplantation of
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31:
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to be transplanted at sites of injury or stress; which is being actively explored for
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1552:10.1016/j.bbmt.2011.07.023
1480:Tissue Engineering. Part A
1293:10.1182/blood-2004-04-1488
1168:10.1016/j.stem.2011.10.010
1008:International Orthopaedics
918:10.1007/s40520-020-01515-1
707:10.1016/j.ando.2010.01.003
537:
512:islet cell transplantation
474:
437:
415:
388:
385:Human embryonic stem cells
377:
362:
293:
266:
39:
29:
2909:10.3389/fmed.2023.1090721
2726:10.1038/s41569-018-0036-6
2065:10.1007/s00586-006-0169-x
1974:10.1186/s13287-018-1051-6
1749:10.1080/14653240902849762
1069:10.1089/ten.teb.2008.0262
1021:10.1007/s00264-018-4223-1
488:graft-versus-host disease
408:and Parkinson's disease.
2489:10.1182/blood.V92.9.3189
2438:(10 Pt 1-2): 1709–1716.
2250:10.3389/fncel.2012.00017
1924:10.1177/1947603514534681
1877:10.1517/14712598.7.2.173
1801:BioProcess International
1655:10.3727/096368910x508762
737:World Journal of Surgery
695:Annales d'Endocrinologie
526:repair by transplanting
412:Neural stem cell therapy
2646:10.1089/scd.2006.15.755
1578:120(11 Suppl): S247–54.
731:Starzl TE (July 2000).
665:American Cancer Society
551:American Cancer Society
458:human leukocyte antigen
454:osteogenesis imperfecta
302:autologous cell therapy
258:Cell therapy strategies
2405:10.1038/sj.bmt.1703650
2059:(Suppl 3): S397–S405.
2053:European Spine Journal
1444:10.3892/ijmm.2018.3454
1345:10.1073/pnas.97.7.3422
794:10.1002/adfm.201707129
152:acute myeloid leukemia
111:
81:cell-mediated immunity
53:
2896:Frontiers in Medicine
1192:Regenerative Medicine
880:(6679 Suppl): 18–24.
749:10.1007/s002680010124
621:Mesenchymal stem cell
616:Regenerative medicine
465:myocardial infarction
440:Mesenchymal stem cell
349:immunogenic responses
224:myocardial infarction
150:and/or radiation for
106:
50:
2147:Nature Biotechnology
2025:10.22203/eCM.v029a15
1643:Cell Transplantation
579:allogeneic therapies
575:CAR T-cell therapies
534:Alternative medicine
520:extracellular matrix
504:differentiated cells
428:Huntington's disease
353:transplant rejection
208:Mechanisms of action
75:capable of fighting
1336:2000PNAS...97.3422K
830:Home.cancerresearch
611:Xenotransplantation
606:Autotransplantation
601:Allotransplantation
524:intervertebral disc
424:Parkinson's disease
391:Embryonic stem cell
365:Xenotransplantation
343:in preventing disc
296:Autotransplantation
269:Allotransplantation
183:articular cartilage
42:Cell Therapy (song)
2949:2016-01-12 at the
2808:"Cellular Therapy"
1807:(suppl. I): 30–37.
968:10.3233/JPD-181488
129:cell encapsulation
112:
91:diseased tissues.
54:
2590:Nature Immunology
2444:10.1172/jci103949
2354:(11): 1607–1614.
2202:10.1159/000101892
2153:(11): 1392–1401.
2108:(11): 1415–1420.
1698:(12): 1617–1624.
1395:10.1002/jsp2.1013
1286:(12): 3581–3587.
1237:(11): 1395–1402.
1204:10.2217/rme.11.28
962:(s1): S131–S137.
782:Adv. Funct. Mater
596:Stem cell therapy
380:Stem cell therapy
83:in the course of
32:Stem cell therapy
16:(Redirected from
2988:
2932:
2931:
2921:
2911:
2887:
2881:
2880:
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2867:
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2859:
2853:
2852:
2845:
2839:
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2837:. ebers Medical.
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2622:
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2585:
2579:
2578:
2558:
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2515:
2509:
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2483:(9): 3189–3202.
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2388:
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2003:
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1465:
1455:
1438:(5): 2553–2564.
1423:
1417:
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1406:
1374:
1368:
1367:
1357:
1347:
1330:(7): 3422–3427.
1315:
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1305:
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1254:
1243:10.1172/jci12150
1222:
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1146:
1140:
1139:
1129:
1097:
1091:
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1080:
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1023:
1014:(4): 1011–1025.
999:
990:
989:
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719:
718:
690:
681:
680:
678:
676:
671:on 26 April 2015
657:
418:Neural stem cell
318:peripheral blood
306:clinical studies
226:, to facilitate
138:, who treated a
136:E Donnall Thomas
21:
18:Cellular therapy
2996:
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2720:(10): 585–600.
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2159:10.1038/nbt1259
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2005:
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1954:
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1155:Cell Stem Cell
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279:pharmaceutical
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861:. 2020-03-21.
860:
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836:on 2020-02-02
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36:Immunotherapy
33:
19:
2976:Cell biology
2899:
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2829:
2819:15 September
2817:. Retrieved
2811:
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2769:(2): 80–94.
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