Breast cancer resistance protein(BCRP/ABCG2):its role in multidrug resistance and regulation of its gene expression

Breast cancer resistance protein(BCRP)/ATP-binding cassette subfamily G member 2(ABCG2) is an ATP-binding cassette(ABC) transporter identified as a molecular cause of multidrug resistance(MDR) in diverse cancer cells.BCRP physiologically functions as a part of a self-defense mechanism for the organism;it enhances elimination of toxic xenobiotic substances and harmful agents in the gut and biliary tract,as well as through the blood-brain,placental,and possibly blood-testis barriers.BCRP recognizes and transports numerous anticancer drugs including conventional chemotherapeutic and targeted small therapeutic molecules relatively new in clinical use.Thus,BCRP expression in cancer cells directly causes MDR by active efflux of anticancer drugs.Because BCRP is also known to be a stem cell marker,its expression in cancer cells could be a manifestation of metabolic and signaling pathways that confer multiple mechanisms of drug resistance,self-renewal(stemness),and invasiveness(aggressiveness),and thereby impart a poor prognosis.Therefore,blocking BCRP-mediated active efflux may provide a therapeutic benefit for cancers.Delineating the precise molecular mechanisms for BCRP gene expression may lead to identification of a novel molecular target to modulate BCRP-mediated MDR.Current evidence suggests that BCRP gene transcription is regulated by a number of trans-acting elements including hypoxia inducible factor 1α,estrogen receptor,and peroxisome proliferator-activated receptor.Furthermore,alternative promoter usage,demethylation of the BCRP promoter,and histone modification are likely associated with drug-induced BCRP overexpression in cancer cells.Finally,PI3K/AKT signaling may play a critical role in modulating BCRP function under a variety of conditions.These biological events seem involved in a complicated manner.Untangling the events would be an essential first step to developing a method to modulate BCRP function to aid patients with cancer.This review will present a synopsis of the impact of BCRP-mediated MDR in cancer cells,and the molecular mechanisms of acquired MDR currently postulated in a variety of human cancers.

EXPRESSION OF BCRP GENE IN THE NORMAL LUNG TISSUE AND LUNG CANCER

Objective: To investigate the expression of novel multidrug resistance transporter (BCRP gene) from human MCF-7/AdrVp breast cancer cells in normal lung tissue and non-small lung cancer tissue. Methods: RNA was extracted immediately from fresh normal lung tissue and viable tumor tissue harvested from surgically resected specimens of non-small cell lung cancer patients. cDNA of BCRP gene was prepared by RT-PCR and was then amplified by PCR. cDNA products from those specimens were transferred to blotting membrane through electrophoresis and transferring technique and southern blot hybridization was eventually performed to detect the expression of BCRP gene. Results: RNA were extracted from 8 tumor tissue alone and 12 pairs of tumor tissue and normal lung tissue harvested from the same lung. Four patients’ RNA samples with poor quality due to degrading were discarded. cDNA products of BCRP gene were obtained by RT-PCR and were then amplified by PCR in the remain 16 patients’ RNA samples. Through southern blot hybridization, BCRP gene was found to be slightly expressed in various amounts in all normal lung tissue (10/10) and only in a half of tumor tissue samples (8/16). Conclusion: BCRP gene is slightly expressed in different amount in all normal lung tissue and only in a half of tumor tissue of non-small cell lung cancer patients. It is possible to induce it’s overexpression and to develop multidrug resistance during chemotherapy if using anthracycline anticancer drugs.

BCRP基因在非小细胞肺癌组织和非癌肺组织中的表达及意义

目的：进一步研究从人类乳腺癌细胞株 (MCF-7/AdrVp)中克隆出的、对蒽环类抗癌药耐药的 BCRP基因在非癌肺组织及非小细胞肺癌组织中的表达。方法：从术后即刻获得的正常肺组织和有活力的非小细胞肺癌组织新鲜标本中及时提取细胞总 RNA，通过 RT-PCR及 PCR法获得并扩增 BCRP基因的 cDNA产物，再经凝胶电泳分离 BCRP基因 cDNA带，然后再通过转膜技术把这些 BCRP基因 cDNA产物转移到杂交膜上，用 Southern blot杂交技术检测 BCRP基因的表达程度。结果：细胞总 RNA分别从 8个只有肺癌组织标本和 12对同时获取的肺癌组织及非癌肺组织标本中成功提取，然后用变性凝胶电泳鉴定提取 RNA的质量。其中 4例标本因术中缺血时间太长，或有坏死炎症或术前放化疗等原因，所提 RNA有降解而放弃进一步的检测。通过 RT-PCR及 PCR方法从 16例可用标本中获得并扩增 BCRP基因的 cDNA产物，再通过转膜及 Southern blot杂交技术，最终发现 BCRP基因在正常肺组织中均有不同程度的表达（ 10/10），而在非小细胞肺癌组织标本中只有一半病人的标本有不同程度的表达 (8/16)。结论： BCRP基因可能是一个在非癌肺组织中常规表达的基因，而在部分病人的肺癌组织中可能此基因有缺失或被抑制。因此。

Lymphoepithelioma-like carcinoma of the breast presenting as breast abscess

Lymphoepithelioma-like carcinoma(LELC) is a rare type of neoplasm in which only twenty cases have been reported in the breast. This type of tumor can be difficult to distinguish from other breast tumors particularly medullary carcinoma and lymphoma in the breast. We present a case of LELC of the breast presenting as an abscess along with a review of the literature. This is the 21 st reported case of LELC of the breast and the first case to present as an abscess. Her clinical picture could have been mistaken for other infectious or inflammatory diseases. Given the potential for favorable outcome, early detection and general knowledge of this neoplasm are essential to expedite treatment for this rare tumor type.

Induced Pluripotent Stem Cell-derived Mesenchymal Stem Cell Seeding on Biofunctionalized Calcium Phosphate Cements

Induced pluripotent stem ceils （iPSCs） have great potential due to their proliferation and differentiation capability. The objectives of this study were to generate iPSC-derived mesenchymal stem cells （iPSC-MSCs）, and investigate iPSC-MSC proliferation and osteogenic differentiation on calcium phosphate cement （CPC） containing biofunctional agents for the first time. Human iPSCs were derived from marrow CD34＋ cells which were reprogrammed by a single episomal vector, iPSCs were cultured to form embryoid bodies （EBs）, and MSCs migrated out of EBs. Five biofunctional agents were incorporated into CPC： RGD （Arg-Gly-Asp） peptides, fibronectin （Fn）, fibronectin-like engineered polymer protein （FEPP）, extracellular matrix Geltrex, and platelet concentrate, iPSC-MSCs were seeded on five biofunctionalized CPCs： CPC-RGD, CPC-Fn, CPC- FEPP, CPC-Geltrex, and CPC-Platelets. iPSC-MSCs on biofunctional CPCs had enhanced proliferation, actin fiber expression, osteogenic differentiation and mineralization, compared to control. Cell proliferation was greatly increased on biofunctional CPCs. iPSC-MSCs underwent osteogenic differentiation with increased alkaline phosphatase, Runx2 and coUagen-I expressions. Mineral synthesis by iPSC-MSCs on CPC-Platelets was 3-fold that of CPC control. In conclusion, iPSCs showed high potential for bone engineering, iPSC- MSCs on biofunctionalized CPCs had cell proliferation and bone mineralization that were much better than traditional CPC. iPSC-MSC-CPC constructs are promising to promote bone regeneration in craniofacial/ orthopedic repairs.

Advanced smart biomaterials and constructs for hard tissue engineering and regeneration

Hard tissue repair and regeneration cost hundreds of billions of dollars annually worldwide, and the need has substantially increased as the population has aged. Hard tissues include bone and tooth structures that contain calcium phosphate minerals.Smart biomaterial-based tissue engineering and regenerative medicine methods have the exciting potential to meet this urgent need. Smart biomaterials and constructs refer to biomaterials and constructs that possess instructive/inductive or triggering/stimulating effects on cells and tissues by engineering the material’s responsiveness to internal or external stimuli or have intelligently tailored properties and functions that can promote tissue repair and regeneration. The smart material-based approaches include smart scaffolds and stem cell constructs for bone tissue engineering; smart drug delivery systems to enhance bone regeneration; smart dental resins that respond to pH to protect tooth structures; smart pH-sensitive dental materials to selectively inhibit acid-producing bacteria; smart polymers to modulate biofilm species away from a pathogenic composition and shift towards a healthy composition; and smart materials to suppress biofilms and avoid drug resistance. These smart biomaterials can not only deliver and guide stem cells to improve tissue regeneration and deliver drugs and bioactive agents with spatially and temporarily controlled releases but can also modulate/suppress biofilms and combat infections in wound sites. The new generation of smart biomaterials provides exciting potential and is a promising opportunity to substantially enhance hard tissue engineering and regenerative medicine efficacy.

Calcium phosphate cements for bone engineering and their biological properties

Calcium phosphate cements （CPCs） are frequently used to repair bone defects. Since their discovery in the 1980s, extensive research has been conducted to improve their properties, and emerging evidence supports their increased application in bone tissue engineering. Much effort has been made to enhance the biological performance of CPCs, including their biocompatibility, osteoconductivity, osteoinductivity, biodegradability, bioactivity, and interactions with cells. This review article focuses on the major recent developments in CPCs, including 3D printing, injectability, stem cell delivery, growth factor and drug delivery, and pre- vascularization of CPC scaffolds via co-culture and tri-culture techniques to enhance angiogenesis and osteogenesis.

EIL-4 protects the B-cell lymphoma cell line CH31 from anti-lgM-induced growth arrest and apoptosis： contribution of the PI-3 kinase/AKT pathway

Interleukin-4 （IL-4） promotes lymphocyte survival and protects primary lymphomas from apoptosls. Previous studies reported differential requirements for the signal transducer and activator of transcription 6 （STAT6） and IRS2/phosphati-dylinositol 3 kinase （PI-3K） signaling pathways in mediating the IL-4-induced protection from Fas-mediated apoptosis. In this study, we characterized IL-4-activated signals that suppress anti-IgM-mediated apoptosis and growth arrest of CH31, a model B-cell lymphoma line. In CH31, anti-IgM treatment leads to the loss of mitochondrial membrane poten-tial, phospho-Akt, phospho-CDK2, and c-myc protein. These losses are followed by massive induction of p27^Kip1 protein expression, cell cycle arrest, and apoptosis. Strikingly, IL-4 treatment prevented or reversed these changes. Furthermore, IL-4 suppressed the activation of caspases 9 and 3, and, in contrast to previous reports, induced the phosphorylation （de-activation） of BAD. IL-4 treatment also induced expression of BclxL, a STAT6-dependent gene. Pharmacologic inhibitors and dominant inhibitory forms of PI-3K and Akt abrogated the anti-apoptotic function of IL-4. These results suggest that the IL-4 receptor activates several signaling pathways, with the Akt pathway playing a major role in suppression of the apoptotic program activated by anti-IgM.

Dental remineralization via poly(amido amine) and restorative materials containing calcium phosphate nanoparticles

Tooth decay is prevalent,and secondary caries causes restoration failures,both of which are related to demineralization.There is an urgent need to develop new therapeutic materials with remineralization functions.This article represents the first review on the cutting edge research of poly(amido amine)(PAMAM) in combination with nanoparticles of amorphous calcium phosphate (NACP).PAMAM was excellent nucleation template,and could absorb calcium (Ca) and phosphate (P) ions via its functional groups to activate remineralization.NACP composite and adhesive showed acid-neutralization and Ca and P ion release capabilities.PAMAM +NACP together showed synergistic effects and produced triple benefits: excellent nucleation templates,superior acidneutralization,and ions release.Therefore,the PAMAM+NACP strategy possessed much greater remineralization capacity than using PAMAM or NACP alone.PAMAM+NACP achieved dentin remineralization even in an acidic solution without any initial Ca and P ions.Besides,the long-term remineralization capability of PAMAM+NACP was established.After prolonged fluid challenge,the immersed PAMAM with the recharged NACP still induced effective dentin mineral regeneration.Furthermore,the hardness of predemineralized dentin was increased back to that of healthy dentin,indicating a complete remineralization.Therefore,the novel PAMAM+NACP approach is promising to provide long-term therapeutic effects including tooth remineralization,hardness increase,and caries-inhibition capabilities.

Effects of water-aging for 6 months on the durability of a novel antimicrobial and protein-repellent dental bonding agent

Biofilms at the tooth-restoration bonded interface can produce acids and cause recurrent caries. Recurrent caries is a primary reason for restoration failures. The objectives of this study were to synthesize a novel bioactive dental bonding agent containing dimethylaminohexadecyl methacrylate(DMAHDM) and 2-methacryloyloxyethyl phosphorylcholine(MPC) to inhibit biofilm formation at the tooth-restoration margin and to investigate the effects of water-aging for 6 months on the dentin bond strength and protein-repellent and antibacterial durability. A protein-repellent agent(MPC) and antibacterial agent(DMAHDM) were added to a Scotchbond multi-purpose(SBMP) primer and adhesive. Specimens were stored in water at 37 °C for 1, 30, 90, or 180 days(d).At the end of each time period, the dentin bond strength and protein-repellent and antibacterial properties were evaluated. Protein attachment onto resin specimens was measured by the micro-bicinchoninic acid approach. A dental plaque microcosm biofilm model was used to test the biofilm response. The SBMP + MPC + DMAHDM group showed no decline in dentin bond strength after water-aging for 6 months, which was significantly higher than that of the control(P < 0.05). The SBMP + MPC + DMAHDM group had protein adhesion that was only 1/20 of that of the SBMP control(P < 0.05). Incorporation of MPC and DMAHDM into SBMP provided a synergistic effect on biofilm reduction. The antibacterial effect and resistance to protein adsorption exhibited no decrease from 1 to 180 d(P > 0.1). In conclusion, a bonding agent with MPC and DMAHDM achieved a durable dentin bond strength and long-term resistance to proteins and oral bacteria. The novel dental bonding agent is promising for applications in preventive and restorative dentistry to reduce biofilm formation at the tooth-restoration margin.

A novel protein-repellent dental composite containing 2-methacryloyloxyethyl phosphorylcholine

Secondary caries due to biofilm acids is a primary cause of dental composite restoration failure.To date,there have been no reports of dental composites that can repel protein adsorption and inhibit bacteria attachment.The objectives of this study were to develop a protein-repellent dental composite by incorporating 2-methacryloyloxyethyl phosphorylcholine（MPC） and to investigate for the first time the effects of MPC mass fraction on protein adsorption,bacteria attachment,biofilm growth,and mechanical properties.Composites were synthesized with 0（control）,0.75%,1.5%,2.25%,3%,4.5%and 6%of MPC by mass.A commercial composite was also tested as a control.Mechanical properties were measured in three-point flexure.Protein adsorption onto the composite was determined by the microbicinchoninic acid method.A human saliva microcosm biofilm model was used.Early attachment at 4 h,biofilm at 2 days,live/dead staining and colony-forming units（CFUs） of biofilms grown on the composites were investigated.Composites with MPC of up to 3%had mechanical properties similar to those without MPC and those of the commercial control,whereas 4.5%and 6%MPC decreased the mechanical properties（P〈0.05）.Increasing MPC from 0 to 3%reduced the protein adsorption on composites（P〈0.05）.The composite with 3%MPC had protein adsorption that was 1/12 that of the control（P〈0.05）.Oral bacteria early attachment and biofilm growth were also greatly reduced on the composite with 3%MPC,compared to the control（P〈0.05）.In conclusion,incorporation of MPC into composites at 3%greatly reduced protein adsorption,bacteria attachment and biofilm CFUs,without compromising mechanical properties.Protein-repellent composites could help to repel bacteria attachment and plaque build-up to reduce secondary caries.The protein-repellent method might be applicable to other dental materials.

Yeast nuclear RNA processing

Nuclear RNA processing requires dynamic and intricately regulated machinery composed of multiple enzymes and their cofactors.In this review,we summarize recent experiments using Saccharomyces cerevisiae as a model system that have yielded important insights regarding the conversion of pre-RNAs to functional RNAs,and the elimination of aberrant RNAs and unneeded intermediates from the nuclear RNA pool.Much progress has been made recently in describing the 3D structure of many elements of the nuclear degradation machinery and its cofactors.Similarly,the regulatory mechanisms that govern RNA processing are gradually coming into focus.Such advances invariably generate many new questions,which we highlight in this review.

Polyplex interaction strength as a driver of potency during cancer immunotherapy

Many experimental cancer vaccines are exploring toll-like receptor agonists （TLRas） such as CpG, a DNA motif that agonizes toll-like receptor 9 （TLR9）, to trigger immune responses that are potent and molecularly-specific. The ability to tune the immune response is especially important in the immunosuppressive microenvironments of tumors. Because TLR9 is located intracellularly, CpG must be internalized by immune cells for functionality. Polyplexes can be self- assembled through electrostatics using DNA （anionic） condensed by a positively charged carrier. These structures improve cell delivery and have been widely explored for gene therapy. In contrast, here we use cationic poly （^-amino esters） （PBAEs） to assemble polyplexes from CpG as an adjuvant to target and improve immune stimulation in cells and mouse models. Polyplexes were formed over a range of PBAE：CpG ratios, resulting in a library of complexes with increasingly positive charge and stronger binding as PBAE：CpG ratio increased. Although higher PBAE：CpG ratios exhibited improved CpG uptake, lower ratios of PBAE：CpG--which condensed CpG more weakly, activated DCs and tumorspecific T cells more effectively. In a mouse melanoma model, polyplexes with lower binding affinities improved survival more effectively compared with higher binding affinities. These data demonstrate that altering the polyplex interaction strength impacts accessibility of CpG to TLRs in immune cells. Thus, physiochemical properties, particularly the interplay between charge, uptake, and affinity, play a key role in determining the nature and efficacy of the immune response generated. This insight identifies new design considerations that must be balanced for engineering effective immunotherapies and vaccines.

Cancer Cell：新型药物组合或有望治疗恶性白血病

近日，刊登在国际杂志Cancer Cell上的一篇研究报告中，来自马里兰大学医学院等机构的研究人员开发了一种新型药物组合或有望帮助治疗急性髓性白血病（AML），在诊断为该疾病后，舭能在5年内使得几乎四分之三的患者死亡。目前在美国三个研究中研究研究人员正在招募研究者进行多中心的临床试验。

Resistance to epidermal growth factor receptor inhibition in non-small cell lung cancer

Aberrant activation of the epidermal growth factor receptor(EGFR)is a driving force for cancer growth in a subgroup of non-small cell lung cancer patients.These patients can be identified by the presence of activating EGFR mutations.Currently three generations of EGFR-tyrosine kinase inhibitors(TKIs)have been approved by the Food and Drug Administration and European Medicine Agency.This paper reviews the structure of EGFR and the downstream signaling pathways of EGFR and describes the mechanisms of intrinsic and acquired resistance against EGFR-TKIs.These mechanisms include secondary or tertiary mutations in EGFR,the activation of bypassing signaling pathways or a histological transformation to small cell lung cancer.Moreover,drug efflux transporters will affect the cellular accumulation of EGFR-TKIs and penetration of the first generation of EGFR-TKI into the brain.Lysosomal sequestration of some EGFR-TKIs may also prevent the drugs to reach their target.In conclusion,resistance to EGFR-TKIs is multifactorial,including primary and acquired mutations in the EGFR gene,activation of bypassing pathways and limited uptake of drugs in the cells or target tissues.More pharmacological studies are needed in order to develop new specific compounds targeted to overcome new resistance mechanisms in order to enable a personalized treatment approach.

Cellular, physiological and pathological aspects of the long non-coding RNA NEAT1

BACKGROUND： The majority of mammalian genomes have been found to be transcribed into non-coding RNAs. One category of non-coding RNAs is classified as long non-coding RNAs （lncRNAs） based on their transcript sizes larger than 200 nucleotides. Growing evidence has shown that lncRNAs are not junk transcripts and play regulatory roles in multiple aspects of biological processes. Dysregulation of lncRNA expression has also been linked to diseases, in particular cancer. Therefore, studies of lncRNAs have attracted significant interest in the field of medical research. Nuclear enriched abundant transcript 1 （NEAT1）, a nuclear lncRNA, has recently emerged as a key regulator involved in various cellular processes, physiological responses, developmental processes, and disease development and progression. OBJECTIVE： This review will summarize and discuss the most recent findings with regard to the roles of NEAT1 in the function of the nuclear paraspeckle, cellular pathways, and physiological responses and processes. Particularly, the most recently reported studies regarding the pathological roles of deregulated NEAT1 in cancer are highlighted in this review. METHODS： We performed a systematic literature search using the Pubmed search engine. Studies published over the past 8 years （between January 2009 and August 2016） were the sources of literature review. The following keywords were used： ＂Nuclear enriched abundant transcript 1,＂ ＂NEATI,＂ and ＂paraspeckles.＂ RESULTS： The Pubmed search identified 34 articles related to the topic of the review. Among the identified literature, 13 articles report findings related to cellular functions of NEAT1 and eight articles are the investigations of physiological functions of NEAT1. The remaining 13 articles are studies of the roles of NEAT1 in cancers. CONCLUSION： Recent advances in NEAT1 studies reveal the multifimctional roles of NEAT1 in various biological processes, which are beyond its role in nuclear paraspeckles. Recent studies also indicate that dysregulation of NEAT1 function contributes to the development and progression of various cancers. More investigations will be needed to address the detailed mechanisms regarding how NEAT1 executes its cellular and physiological functions and how NEAT1 dysregulation results in tumorigenesis, and to explore the potential of NEAT1 as a target in cancer diagnosis, prognosis and therapy.

The Interferon Signaling Network and Transcription Factor C/EBP-β

Cytokines like interferons （IFNs） play a central role in regulating innate and specific immunities against the pathogens and neoplastic cells. A number of signaling pathways are induced in response to IFN in various cells. One classic mechanism employed by IFNs is the JAK-STAT signaling pathway for inducing cellular responses. Here we describe the non-STAT pathways that participate in IFN-induced responses. In particular, we will focus on the role played by transcription factor C/EBP-β in mediating these responses. Cellular ＆ Molecular Immunology.

Inhibition of CCL2 by bindarit alleviates diabetes-associated periodontitis by suppressing inflammatory monocyte infiltration and altering macrophage properties

Diabetes-associated periodontitis(DP)aggravates diabetic complications and increases mortality from diabetes.DP is caused by diabetes-enhanced host immune-inflammatory responses to bacterial insult.In this study,we found that persistently elevated CCL2 levels in combination with proinflammatory monocyte infiltration of periodontal tissues were closely related to DP.Moreover,inhibition of CCL2 by oral administration of bindarit reduced alveolar bone loss and increased periodontal epithelial thickness by suppressing periodontal inflammation.Furthermore,bindarit suppressed the infiltration of proinflammatory monocytes and altered the inflammatory properties of macrophages in the diabetic periodontium.This finding provides a basis for the development of an effective therapeutic approach for treating DP.

Rock inhibitor may compromise human induced pluripotent stem cells for cardiac differentiation in 3D

Cardiomyocytes differentiated from human induced pluripotent stem cells(iPSCs)are valuable for the understanding/treatment of the deadly heart diseases and their drug screening.However,the very much needed homogeneous 3D cardiac differentiation of human iPSCs is still challenging.Here,it is discovered surprisingly that Rock inhibitor(RI),used ubiquitously to improve the survival/yield of human iPSCs,induces early gastrulation-like change to human iPSCs in 3D culture and may cause their heterogeneous differentiation into all the three germ layers(i.e.,ectoderm,mesoderm,and endoderm)at the commonly used concentration(10μM).This greatly compromises the capacity of human iPSCs for homogeneous 3D cardiac differentiation.By reducing the RI to 1μM for 3D culture,the human iPSCs retain high pluripotency/quality in inner cell mass-like solid 3D spheroids.Consequently,the beating efficiency of 3D cardiac differentiation can be improved to more than 95%in~7 days(compared to less than~50%in 14 days for the 10μM RI condition).Furthermore,the outset beating time(OBT)of all resultant cardiac spheroids(CSs)is synchronized within only 1 day and they form a synchronously beating 3D construct after 5-day culture in gelatin methacrylol(GelMA)hydrogel,showing high homogeneity(in terms of the OBT)in functional maturity of the CSs.Moreover,the resultant cardiomyocytes are of high quality with key functional ultrastructures and highly responsive to cardiac drugs.These discoveries may greatly facilitate the utilization of human iPSCs for understanding and treating heart diseases.

Sand-mediated ice seeding enables serum-free low-cryoprotectant cryopreservation of human induced pluripotent stem cells

Human induced pluripotent stem cells(hiPSCs)possess tremendous potential for tissue regeneration and banking hiPSCs by cryopreservation for their ready availability is crucial to their widespread use.However,contemporary methods for hiPSC cryopreservation are associated with both limited cell survival and high concentration of toxic cryoprotectants and/or serum.The latter may cause spontaneous differentiation and/or introduce xenogeneic factors,which may compromise the quality of hiPSCs.Here,sand from nature is discovered to be capable of seeding ice above10◦C,which enables cryopreservation of hiPSCs with no serum,much-reduced cryoprotectant,and high cell survival.Furthermore,the cryopreserved hiPSCs retain high pluripotency and functions judged by their pluripotency marker expression,cell cycle analysis,and capability of differentiation into the three germ layers.This unique sand-mediated cryopreservation method may greatly facilitate the convenient and ready availability of high-quality hiPSCs and probably many other types of cells/tissues for the emerging cell-based translational medicine.