Current status and perspectives on stem cell-based therapies undergoing clinical trials for regenerative medicine: case studies

Ratcliffe, Elizabeth; Glen, Katie E.; Naing, May Win; Williams, David J.

doi:10.1093/bmb/ldt034

Cited by 70 publications

(51 citation statements)

References 46 publications

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“…Said to be the fourth therapeutic pillar of healthcare (Mason et al, 2011) and with induced pluripotent stem cells touted to be "a game changer" (Inoue et al, 2014), the cell therapy industry continues to grow and is estimated to reach an annual turnover of $20bn worldwide by 2025 (Cell Therapy Catapult website). Recent years have seen clinical trials show signs of success (Ratcliffe et al, 2013a) and products such as Prochymal (Osiris Therapeutics Inc) and ChondroCelect (TiGenix) gain regulatory approval. However, many new cell therapies are treating relatively small numbers of patients so a universal system for delivery of these products from the site of manufacture to the clinic has not yet been established.…”

Section: Introductionmentioning

confidence: 99%

From production to patient: challenges and approaches for delivering cell therapies

Coopman

Medcalf

2014

StemBook

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Section: Introductionmentioning

confidence: 99%

From production to patient: challenges and approaches for delivering cell therapies

Coopman

Medcalf

2014

StemBook

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“…GVHD is a cause of high mortality in recipients of allogenic transplants. Prochymal MSC is the first stem cell therapy approved for treatment of steroid resistant, acute GVHD in pediatric patients reducing transplant related mortality and high survival rates [15]. The immunosuppressive property of MSC has also been employed for treatment of relapsing and remitting MS.…”

Section: Diseases For Which Stem Cell Trans-plantation Has Been Usedmentioning

confidence: 99%

Stem Cells in Regenerative Medicine: Prospects and Pitfalls

Zehravi¹,

Shahid²,

Kashmala³

et al. 2017

Natl. j. health sci.

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Stem cells are the cells that have the ability to regenerate themselves and are able to differentiate into one or more specialized cell types. This unique property makes them a valuable source for in vitro disease modeling, drug designing, regenerative medicine and tissue engineering. As no specie can fully mimic the human microenvironment, human cell models derived from patients cells provide a fascinating avenue for enhancing our current understanding of the early molecular stages of various diseases followed by validating therapeutics. In this paper, we reviewed the role of stem cells in regenerative medicine that includes use of cord blood derived stem cells in medicine and patient specific induced pluripotent stem cells for future transplant purposes and the hurdles and obstacles that we need to address before we can safely use these cells for patient cure.

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“…Judious application of re-programming may lead towards establishing a UCB derived iPSC bank in the future. Some stem cell products are already about to reach clinic such as iPSC for macular regeneration which was discovered by Takahashi and collaborates [82]. In vivo infusion of ex vivo expanded "off the shelf" non HLA matched UCB products are also currently tested under a Phase II clinical trial (NCT 01175785) conducted by Fred Hutchinson Cancer Center.…”

Section: Conclusion and Final Remarksmentioning

confidence: 99%

“…More pre-clinical and clinical data is needed for optimizing the kinetics of CB cellular immune therapies. Transplantation of ex vivo expanded UCB cells is becoming a reality, while the issue of expanded cell banking emerges as an option allowing the conservation of the product for future use [82]. Widespread application can only be achieved via robust expansion.…”

Section: Conclusion and Final Remarksmentioning

confidence: 99%

Modalities to Improve Cord Blood Engraftment

Yurdakul¹

2014

J Stem Cell Res Ther

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Umblical cord blood (UCB) is one of the major sources of Hematopoietic Stem Cell Transplantation (HSCT) with increasing use in clinical practice. UCB can be a life saver for patients who do not have a matched unrelated adult donor or for patients who are in need of an urgent transplantation. Various factors make UCB a significant source of Hematopoietic Stem Cells (HSCs), including ease of procurement and lack of donor attrition, with the ability to process and long term storage of donor cells. Importantly, UCB donations can be used right away without the need for a "perfect" HLA match, thereby increasing donor access to HSCT, particularly for minority and mixed ethnicity patients, for whom a suitably matched related or unrelated donor may be difficult to locate. The major limitation of UCB is the quantity of cells to be infused. Although high proliferative potential allows one log less use of HSCs (HSC<10 5 /kg) compared to bone marrow (BM) or peripheral blood mononuclear cells (PBSC), even this amount cannot be reached in the majority of patients under donor search. When total nucleated cell (TNC) and CD34+ cell doses in UCB grafts are analyzed, a high correlation is observed with the rate of neutrophil and platelet engraftment, the incidence of graft failure and early transplant-related complications. It has been shown that UCB grafts with more than 3/6 HLA mismatches and with cell doses under the defined minimum threshold lead to higher transplantation related mortality (TRM). Especially when adult cord blood transplantation (UCBT) is the subject, providing units with enough cells remains the major drawback.Despite certain efforts, there is still an unmet need for increasing HSC cell dose and/or stimulating engraftment without loss of their long term repopulating (LTR) potential and reducing graft versus host disease (GVHD). Intrinsic and extrinsic cellular factors have been proven to act roles in HSC expansion thus justifying their role in in vitro and ex vivo culture conditions. Attempts to regulate these factors through ex vivo expansion methods aim to overcome insufficient cell numbers while methods promoting HSC homing is in favor of the latter. Combination of both appear to work synergistically. Induction or adoptive transfer of UCB derived immune cells particularly Natural Killer (NK) cells and regulatory T cells (T reg) with or without cytokines are also effective approaches for gaining better engraftment levels after UCBT. All of these approaches have been denoted as "successful" in pre-clinical in vitro and animal studies. Many of them have also been tested in early/later phase clinical trials resulting in encouraging results. We aim to review the current knowledge on UCB expansion and engraftment enhancer methods, a very rapidly improving field particularly in the last decade.Eltrombopag enhanced expansion of HSC/HPC of human UCB in vivo and in vitro, and promoted multi-lineage hematopoiesis through the expansion of BM HSC/HPC of human UCB in vivo. A novel c-MPL agonist, a small molecule, ...

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Current status and perspectives on stem cell-based therapies undergoing clinical trials for regenerative medicine: case studies

Abstract: The field is growing year on year with the first clinical trial using induced pluripotent stem cells anticipated by end 2013.

Cited by 70 publications

References 46 publications

From production to patient: challenges and approaches for delivering cell therapies

From production to patient: challenges and approaches for delivering cell therapies

Stem Cells in Regenerative Medicine: Prospects and Pitfalls

Modalities to Improve Cord Blood Engraftment

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