Abstract:
BACKGROUND:Hematopoietic stem cell (HSC) transplantation has been widely applied to the treatment of malignant blood diseases. However, limited number of functional HSCs hinders successful transplantation. The purpose of our current study is to develop a new and cost-efficient medium formulation that could greatly enhance the expansion of HSCs while retaining their long-term repopulation and hematopoietic properties for effective clinical transplantation. METHODS:Enriched human CD34+ cells and mobilized nonhuman primate peripheral blood CD34+ cells were expanded with a new, cost-efficient expansion medium formulation, named hematopoietic expansion medium (HEM), consisting of various cytokines and nutritional supplements. The long-term repopulation potential and hematologic-lineage differentiation ability of expanded human cells were studied in the non-obese diabetic/severe combined immunodeficiency mouse model. Furthermore, the efficacy and safety studies were performed by autologous transplantation of expanded primate cells in the nonhuman primate model. RESULTS:HEM could effectively expand human CD34+ cells by up to 129 fold within 9 days. Expanded HSCs retained long-term repopulation potential and hematologic-lineage differentiation ability, as indicated by (1) maintenance (over unexpanded HSCs) of immunophenotypes of CD38-CD90+CD45RA-CD49f+ in CD34+ cells after expansion; (2) significant presence of multiple human hematopoietic lineages in mouse peripheral blood and bone marrow following primary transplantation; (3) enrichment (over unexpanded HSCs) in SCID-repopulating cell frequency measured by limiting dilution analysis; and (4) preservation of both myeloid and lymphoid potential among human leukocytes from mouse bone marrow in week 24 after primary transplantation or secondary transplantation. Moreover, the results of autologous transplantation in nonhuman primates demonstrated that HEM-expanded CD34+ cells could enhance hematological recovery after myelo-suppression. All primates transplanted with the expanded autologous CD34+ cells survived for over 18 months without any noticeable abnormalities. CONCLUSIONS:Together, these findings demonstrate promising potential for the utility of HEM to improve expansion of HSCs for clinical application.
journal_name
Stem Cell Res Therjournal_title
Stem cell research & therapyauthors
Zhang Y,Shen B,Guan X,Qin M,Ren Z,Ma Y,Dai W,Ding X,Jiang Ydoi
10.1186/s13287-019-1275-0subject
Has Abstractpub_date
2019-06-13 00:00:00pages
173issue
1issn
1757-6512pii
10.1186/s13287-019-1275-0journal_volume
10pub_type
杂志文章abstract:BACKGROUND:In a previous study, we demonstrated that intravenous administration of adipose tissue stem cells (ASCs) could significantly reduce allergic symptoms and suppress eosinophilic inflammation. METHODS:To evaluate the secretome of ASCs, we administrated culture supernatant of ASCs (ASC sup, which contains the A...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-016-0462-5
更新日期:2017-01-23 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-015-0104-3
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/scrt436
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journal_title:Stem cell research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13287-020-01857-7
更新日期:2020-08-12 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-018-0861-x
更新日期:2018-04-19 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-017-0752-6
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-015-0043-z
更新日期:2015-05-09 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-016-0410-4
更新日期:2016-09-29 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
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doi:10.1186/s13287-020-02092-w
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journal_title:Stem cell research & therapy
pub_type: 杂志文章,评审
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abstract:INTRODUCTION:Fallopian tube, which is normally discarded in surgical procedures, has proven to be a source of mesenchymal stem cells (MSCs) with increasing evidence. However, fallopian tube mucosa, which can be acquired via non-invasive procedures, is a previously unknown source of MSCs. In the present study, we explor...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-015-0094-1
更新日期:2015-05-21 00:00:00
abstract:BACKGROUND:Stem cells from human exfoliated deciduous teeth (SHED) have recently attracted attention as novel multipotential stem cell sources. However, their application is limited due to in vitro replicative senescence. Ectopic expression of telomerase reverse transcriptase (TERT) is a promising strategy for overcomi...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-016-0309-0
更新日期:2016-04-04 00:00:00
abstract:INTRODUCTION:Mesenchymal stromal cells (MSCs) play an important role in the prevention of cell and tissue fibrosis. Senescence may decrease the function of MSCs during recovery from tissue and organ damage. Extracellular vesicles (EVs) released from MSCs contribute to the repair of kidney injury. We explored the influe...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01792-7
更新日期:2020-07-08 00:00:00
abstract:BACKGROUND:Many factors may influence the efficacy of cell therapy for intrinsic urinary sphincter deficiency (ISD), including the route of administration of the cells and the condition of the sphincter. The goal of this study was to compare local versus intravenous administration of autologous skeletal muscle precurso...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-016-0411-3
更新日期:2016-10-07 00:00:00
abstract:BACKGROUND:Autologous grafting, despite some disadvantages, is still considered the gold standard for reconstruction of maxillofacial bone defects. The aim of this study was to evaluate bone regeneration using bone marrow-derived mesenchymal stromal cells (MSCs) in a clinical trial, a less invasive approach than autolo...
journal_title:Stem cell research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/s13287-018-0951-9
更新日期:2018-08-09 00:00:00
abstract::Stem cell-based therapies raise hope for cell replacement and provide opportunity for cardiac regenerative medicine and tumor therapy. Extracellular vesicles are a membrane-enclosed intercellular delivery system with the potential to improve the therapeutic efficacy of the treatment of a variety of disorders. As the i...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-019-1417-4
更新日期:2019-10-29 00:00:00
abstract:BACKGROUND:Bone marrow mesenchymal stem cells (BMSC) transfer has been attempted as a therapeutic strategy in experimental lung injury and fibrosis. Reduction of neutrophilic infiltration is one of the mechanisms involved in this effect. However, the mechanisms by which BMSC modulate neutrophil remains unknown. METHOD...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-018-0983-1
更新日期:2018-09-26 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01891-5
更新日期:2020-09-03 00:00:00
abstract::The role of p53 as "a guardian of the genome" has been well established in somatic cells. However, its role in pluripotent stem cells remains much more elusive. Here, we discuss research progress in understanding the role of p53 in pluripotent stem cells and in pluripotent stem cell-like cancer stem cells. The p53 pro...
journal_title:Stem cell research & therapy
pub_type: 杂志文章,评审
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journal_title:Stem cell research & therapy
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journal_title:Stem cell research & therapy
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doi:10.1186/scrt422
更新日期:2014-03-14 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-017-0577-3
更新日期:2017-05-25 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-018-0786-4
更新日期:2018-02-21 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13287-020-01783-8
更新日期:2020-07-21 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-018-0923-0
更新日期:2018-07-04 00:00:00
abstract:BACKGROUND:Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal cells currently tested for multiple therapeutic purposes. Their potential to home into tumors, to secrete trophic/vasculogenic factors, and to suppress immune response raises questions regarding their biosafety. Our aim was to evaluate wheth...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-018-0878-1
更新日期:2018-05-11 00:00:00
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journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/scrt396
更新日期:2014-01-14 00:00:00
abstract:BACKGROUND:The Activin A and bone morphogenetic protein (BMP) pathways are critical regulators of the immune system and of bone formation. Inappropriate activation of these pathways, as in conditions of congenital heterotopic ossification, are thought to activate an osteogenic program in endothelial cells. However, if ...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-016-0372-6
更新日期:2016-08-17 00:00:00
abstract::Because of their multi/pluripotency and immunosuppressive properties, mesenchymal stem/stromal cells (MSCs) are important tools for treating immune disorders and for tissue repair. The increasing use of MSCs, their definition as advanced-therapy medicinal products in European regulations, and the US Food and Drug Admi...
journal_title:Stem cell research & therapy
pub_type: 杂志文章,评审
doi:10.1186/scrt217
更新日期:2013-06-07 00:00:00