Is MSCs Transplantation Safe clinically?

JOEL

* E) G! a6 q* F5 S/ |4 l4 ~Some of the professionals in China have been holding that MSCs transplantation is safe the potential risks can be ignored. "IS THAT TRUE?" Please to read the following information from the authoratative institutes.
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& j$ ]4 N6 y9 Z3 CPotential risks of use of MSCs
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/ }! J$ Q9 p- p, \Because of the differentiation potentials, immunosuppressive properties and some possible immortalisation/transformation during long-term culture of MSCs, their use could imply different risks. Recently, MSCs injected into rat hearts were shown to drive to calcification and possibly differentiate into unwanted tissues such as bone [120]. Most importantly, recent concerns have been expressed about the potential transformation of MSCs during the culture process. As was shown recently, the transformation of human MSCs can occur in cells cultured for a long time [121]. The transformation of MSCs in culture is a multistep process that takes a long time. The first steps involve a surexpression of c-myc, a deletion of p16ink4a that normally drives cells to senescence, and finally a re-expression of hTERT [121]. However, MSCs cultured for a normal duration and reaching < 25 population doublings never undergo transformation [122]. In vivo, MSCs were found to help with tumour development [121]. This effect could be explained by their immunosuppressive properties and the development of a permissive stroma for the tumour, as was demonstrated in myeloma [123,124]. MSCs have been used in clinical trials since 1995; currently, more than 80 trials are registered with ClinicalTrials.gov and no significant adverse events have been reported. However, all these risks imply the use of animal models before MSCs are used in humans and to the implementation of relevant controls (see below Controls for clinically produced MSCs) for clinical-grade MSCs.
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3 ~. g! J7 @! x7 H: sProducing MSCs for clinical applications: European and U.S. Legal Framework0 O# n# H1 z7 x" F2 C- ]9 H4 ~

7 G. f3 k# o, J' n5 L$ s7 p. cIn Europe, MSCs are considered advanced therapy medicinal products (ATMPs), as defined by the European Regulation (European Commission [EC]) No. 1394/2007 (http://eur-lex.europa.eu/LexUriS ... do?uri=OJ), which was enforced on December 30, 2008, without any need for further national implementation laws. ATMPs include the following:
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, `0 m4 k9 V; `      Gene therapy medicinal products, as defined in Part IV of Annex I to Directive 2001/83/EC (DIRECTIVE 2001/83/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 6 November 2001 on the Community code relating to medicinal products for human use: OJ L 311, 67)7 S1 m& N0 m) H' w+ z) S9 z
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( B1 x6 F, m2 N" ~. U0 Y& p: F5 r     Somatic cell therapy medicinal products, as defined in Part IV of Directive 2001/83/EC( V3 I( V6 g' c
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      Tissue-engineered products, intended products that contain or consist of engineered cells or tissues and have properties for or are administered to human beings to regenerate, repair or replace human tissues/ K0 K- `; t% e/ l
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Cells or tissues are considered ‘engineered’ if they fulfill at least one of the following conditions:
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3 n: I3 e' N  G7 q      The cells or tissues have undergone substantial manipulation to achieve biological characteristics, physiological functions or structural properties relevant for the intended regeneration, repair or replacement. The following manipulations are not considered ‘substantial manipulation’: cutting, grinding, shaping, centrifugation, soaking in antibiotic or antimicrobial solutions, sterilization, irradiation, cell separation, concentration or purification, filtering, lyophilisation, freezing, cryopreservation, or vitrification.3 j. Q4 O. K. i/ T' N# l. B
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      The cells or tissues are not intended to be used for the same functions in the recipient as in the donor (‘non-homologous use’).; `! h9 Q7 f' E+ V- Y3 f

% u% y# Z% {! d& m8 w$ `& Q# v5 YTherefore, under European Regulation (EC) No. 1394/2007, MSCs are considered somatic-cell therapy products or tissue-engineered products depending on the source, manufacturing process and proposed indications. European Regulation (EC) No. 1394/2007 contains rules for authorization, supervision and technical requirements regarding the summary of product characteristics, labeling and the package leaflet of ATMPs that are prepared following industrial methods and in academic institutions. The regulation refers to the European GMP rules (http://ec.europa.eu/enterprise/p ... udralex/vol4_en.htm). The only exception is custom-made (hospital) ATMPs, which are prepared on a non-routine basis according to specific quality standards. Such ATMPs are used within the same member state in a hospital under exclusive professional responsibility of a medical practitioner to comply with a medical prescription for a custom-made product for an individual patient.6 O  k& B9 e$ g$ Z4 T
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The EU Regulation is in compliance with the 2004/23/EC directive on donation, procurement and testing of human cells and tissues (http://europa.eu/eur-lex/pri/en/ ... 40407en00480058.pdf) and with directive 2002/98/EC on human blood and blood components (http://eur-lex.europa.eu/LexUriS ... do?uri=OJ). Moreover, a specific article of the EU Regulation is dedicated to traceability, which is of particular interest for MSCs because their expansion potential makes them a reliable ‘off-the-shelf’ cellular product for use in multiple recipients.2 i4 P) ]6 B, D9 C* @& l% [9 Q% t6 {

) @8 {, E% C0 n+ v# pIn the United States, MSCs are considered in the context of human cells, tissues, or cellular and tissue-based products (HCT/Ps). As for any other HCT/Ps, MSC production must comply with Current Good Tissue Practice (CGTP) requirements, under The Code of Federal Regulation (CFR), Title 21, Part 1271 (21 CFR Part 1271) (http://www.access.gpo.gov/nara/cfr/waisidx_08/21cfr1271_08.html). The essential CGTP requirements are related to preventing the introduction, transmission, or spread of communicable disease by HCT/Ps and cover the following:$ j6 Y. s0 Q9 v- B) R
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2 Z2 r& I: D0 G+ |) e3 w     facilities (Part 1271.190a and b)" _- `7 Y5 R& c
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8 y- Q0 g$ C& S* ]" B# ^* j     environmental control (Part 1271.195a)
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2 U0 v# }5 ^# F     equipment (Part 1271.200a)
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     supplies and reagents (Part 1271.210a and b): |5 Y3 N1 c. }- |
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% T% X" b- w; ^3 E% C( Y+ z     recovery (Part 1271.215)3 [9 F& F" j. d3 \( X
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     processing and process controls (Part 1271.220)# m8 u2 z* o1 I
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     labeling controls (Part 1271.250a and b)
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     storage (Part 1271.260a–d)1 B. [4 R* D+ ?- ?8 a1 G
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     receipt, predistribution shipment and distribution of an HCT/P (Part 1271.265a–d)
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     donor eligibility determinations, donor screening and donor testing (Parts 1271.50, 1271.75, 1271.80 and 1271.85)& e0 L( \. W4 \) V9 x# B
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To introduce MSCs or deliver them for introduction for clinical use, as a drug that is also a biological product, a valid biologics license (BLA) must be in effect. Such licenses are issued only after the product has been shown to be safe and efficacious for its intended use. While in the development stage, such products may be distributed for clinical use for humans only if the sponsor has an investigational new drug (IND) application in effect as specified by Food and Drug Administration (FDA) regulations (21 CFR Part 312). Under 21 CFR Part 1271, HCT/Ps are not subject to licensure or IND requirements if certain criteria are met (21 CFR Part 1271.10). These criteria are not met if MSCs are intended for non-homologous use (21 CFR Part 1271.10(a)[2]; 21 CFR part 1271.3c), even though the definition of homologous use for MSCs is still a matter of debate. In January 2009, the FDA released for public comment a draft ‘Guidance for Industry on Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues and Cellular and Tissue-based Products’ (http://www.fda.gov/Cber/gdlns/tissuehctps.pdf) to provide recommendations for complying with CGTP to manufacturers of HCT/Ps.

JOEL

' [" Z$ N  `) `& V) B# @. c, GThe source above is answering the question---
& y3 H& k% j9 K4 B; E& L3 y, C2 `Is that true that MSCs Transplantation is without any risk???  ---the answer is NO absolutely! : [+ F% C  |+ V5 d
One who knows the truth but lies intentionally to the public is a lier and a criminal！
9 @* g9 z' x2 r8 W% y  ?上文回答這样的問題---
  w! h# S  N: R: w% `) _$ m“間充貭干细胞临床移植没有任何風險” 這是眞的嗎？？？---回答：絶對不是。  K" l6 z: m: w
因爾明知實况謊言欺衆者，則是---彻頭彻尾的謊者和罪犯！
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: A1 ~  L: O$ p" p. ?Chinese Friend‘s 精彩编者按： 由於SCR（干细胞研究）使得貴G科學家這一桂冠光彩不再。科学家自己首先是人。很遗憾，人們惊讶地發現，竟有些雖 IQ 颇高於人，却是“亚人种”， 甚者是“非人种” 因爲有他們自己的行爲和操守爲證。君不知， 那些荣獲公衆推举被冠以“薄死”，“钻家”，“叫兽” “坑爷家” 之流是也。