Chitosan/collagen/Mg, Se, Sr, Zn-substituted calcium phosphate scaffolds for bone tissue engineering applications : A growth factor free approach

According to the biomimetic bone scaffold design paradigm, a scaffold resembling natural bone tissue with molecular, structural and biological compatibility is needed to allow effective regeneration of bone tissue. Continuing our previous studies regarding scaffolds with chitosan matrix containing Mg, Se, Sr, Zn-substituted calcium phosphates (CaPs), the focus of this work was to further improve the properties of these growth factor-free scaffolds. By addition of collagen into the chitosan matrix at weight ratios of 100:0, 75:25, 50:50, 25:75 and 0:100, we aimed to better resemble natural bone tissue. Highly porous composite scaffolds based on chitosan and collagen, with 30 wt% of Mg, Se, Sr, Zn-substituted CaPs, were prepared by the freeze-gelation method. The scaffolds show a highly porous structure, with interconnected pores in the range of 20–350 μm and homogeneously dispersed CaPs. The added collagen further enhanced the stability measured during 28 days in simulated biological conditions. Live/dead and CyQUANT assays confirmed good viability and proliferation of human bone marrow-derived mesenchymal stem/stromal cells, while successful osteogenic differentiation was confirmed by alkaline phosphatase quantification and type I collagen immunocytochemical staining. Results indicated that the addition of collagen into the chitosan matrix containing Mg, Se, Sr, Zn-substituted CaPs improved the physicochemical and biological properties of the scaffolds.publishedVersionPeer reviewe

Growth Response and Differentiation of Bone Marrow-Derived Mesenchymal Stem/Stromal Cells in the Presence of Novel Multiple Myeloma Drug Melflufen

Mesenchymal stem/stromal cells (MSCs) are self-renewing and multipotent progenitors, which constitute the main cellular compartment of the bone marrow stroma. Because MSCs have an important role in the pathogenesis of multiple myeloma, it is essential to know if novel drugs target MSCs. Melflufen is a novel anticancer peptide-drug conjugate compound for patients with relapsed refractory multiple myeloma. Here, we studied the cytotoxicity of melflufen, melphalan and doxorubicin in healthy human bone marrow-derived MSCs (BMSCs) and how these drugs affect BMSC proliferation. We established co-cultures of BMSCs with MM.1S myeloma cells to see if BMSCs increase or decrease the cytotoxicity of melflufen, melphalan, bortezomib and doxorubicin. We evaluated how the drugs affect BMSC differentiation into adipocytes and osteoblasts and the BMSC-supported formation of vascular networks. Our results showed that BMSCs were more sensitive to melflufen than to melphalan. The cytotoxicity of melflufen in myeloma cells was not affected by the co-culture with BMSCs, as was the case for melphalan, bortezomib and doxorubicin. Adipogenesis, osteogenesis and BMSC-mediated angiogenesis were all affected by melflufen. Melphalan and doxorubicin affected BMSC differentiation in similar ways. The effects on adipogenesis and osteogenesis were not solely because of effects on proliferation, seen from the differential expression of differentiation markers normalized by cell number. Overall, our results indicate that melflufen has a significant impact on BMSCs, which could possibly affect therapy outcome.Peer reviewe

Growth Response and Differentiation of Bone Marrow-Derived Mesenchymal Stem/Stromal Cells in the Presence of Novel Multiple Myeloma Drug Melflufen

Mesenchymal stem/stromal cells (MSCs) are self-renewing and multipotent progenitors, which constitute the main cellular compartment of the bone marrow stroma. Because MSCs have an important role in the pathogenesis of multiple myeloma, it is essential to know if novel drugs target MSCs. Melflufen is a novel anticancer peptide–drug conjugate compound for patients with relapsed refractory multiple myeloma. Here, we studied the cytotoxicity of melflufen, melphalan and doxorubicin in healthy human bone marrow-derived MSCs (BMSCs) and how these drugs affect BMSC proliferation. We established co-cultures of BMSCs with MM.1S myeloma cells to see if BMSCs increase or decrease the cytotoxicity of melflufen, melphalan, bortezomib and doxorubicin. We evaluated how the drugs affect BMSC differentiation into adipocytes and osteoblasts and the BMSC-supported formation of vascular networks. Our results showed that BMSCs were more sensitive to melflufen than to melphalan. The cytotoxicity of melflufen in myeloma cells was not affected by the co-culture with BMSCs, as was the case for melphalan, bortezomib and doxorubicin. Adipogenesis, osteogenesis and BMSC-mediated angiogenesis were all affected by melflufen. Melphalan and doxorubicin affected BMSC differentiation in similar ways. The effects on adipogenesis and osteogenesis were not solely because of effects on proliferation, seen from the differential expression of differentiation markers normalized by cell number. Overall, our results indicate that melflufen has a significant impact on BMSCs, which could possibly affect therapy outcome

Growth Response and Differentiation of Bone Marrow-Derived Mesenchymal Stem/Stromal Cells in the Presence of Novel Multiple Myeloma Drug Melflufen

Mesenchymal stem/stromal cells (MSCs) are self-renewing and multipotent progenitors, which constitute the main cellular compartment of the bone marrow stroma. Because MSCs have an important role in the pathogenesis of multiple myeloma, it is essential to know if novel drugs target MSCs. Melflufen is a novel anticancer peptide–drug conjugate compound for patients with relapsed refractory multiple myeloma. Here, we studied the cytotoxicity of melflufen, melphalan and doxorubicin in healthy human bone marrow-derived MSCs (BMSCs) and how these drugs affect BMSC proliferation. We established co-cultures of BMSCs with MM.1S myeloma cells to see if BMSCs increase or decrease the cytotoxicity of melflufen, melphalan, bortezomib and doxorubicin. We evaluated how the drugs affect BMSC differentiation into adipocytes and osteoblasts and the BMSC-supported formation of vascular networks. Our results showed that BMSCs were more sensitive to melflufen than to melphalan. The cytotoxicity of melflufen in myeloma cells was not affected by the co-culture with BMSCs, as was the case for melphalan, bortezomib and doxorubicin. Adipogenesis, osteogenesis and BMSC-mediated angiogenesis were all affected by melflufen. Melphalan and doxorubicin affected BMSC differentiation in similar ways. The effects on adipogenesis and osteogenesis were not solely because of effects on proliferation, seen from the differential expression of differentiation markers normalized by cell number. Overall, our results indicate that melflufen has a significant impact on BMSCs, which could possibly affect therapy outcome

Management practices, human capital, and productivity

Väitöskirja sisältää kolme johtamiskäytäntöjen taloustiedettä ja tuottavuutta käsittelevää tutkimusartikkelia. Ensimmäisessä artikkelissa tarkastellaan johtamiskäytäntöjen vaihtelua maittain ja alueittain. Määrällisin menetelmin mitattujen johtamiskäytäntöpistemäärien perusteella Suomen teollisuuden johtamiskäytännöt vaikuttavat olevan vain vähän heikommat kuin Yhdysvalloissa ja samaa tasoa Saksan kanssa. Suomen sisäisissä alueellisissa vertailuissa havaittiin vaihtelua työvoiman määrällä painotetuissa keskiarvoissa, mutta ei painottamattomissa keskiarvoissa. Erot työvoiman kohdentumisessa saattavat siis selittää alueellisia eroavuuksia Suomessa. Työvoiman kohdentumisen tarkempaan tutkimiseen hyödynnetään momenttiestimaattoreihin perustuvaa menetelmää, joka mahdollistaa keskivirheiden laskemisen ja tilastollisten hypoteesien testauksen Olley Pakes -hajotelman osille. Menetelmän avulla havaittiin viitteitä kilpailukyvyn kannalta relevantin allokaatiovaikutuksen alueellisista eroista. Toisessa artikkelissa tutkitaan johtajien inhimillisen pääoman yhteyttä tuottavuuden ja johtamiskäytäntöjen väliseen suhteeseen. Tulosten perusteella strukturoitujen johtamiskäytäntöjen käyttöönottoon liittyvät tuottavuusparannukset riippuvat johtajien inhimillisen pääoman määrästä. Kun tämä interaktio on otettu huomioon, kymmenen prosenttia korkeampi johtamiskäytäntöpistemäärä on yhteydessä keskimäärin 7,1 prosenttia korkeampaan työn tuottavuuteen. Johtamiskäytännöt voivat selittää jopa 24 prosenttia havaitusta tuottavuusvaihtelusta, mikä on lähes yhtä suuri selitysosuus kuin tieto- ja viestintätekniikalla ja suurempi kuin tutkimus- ja kehittämistoiminnalla sekä inhimillisellä pääomalla. Viimeinen artikkeli tarkastelee työntekijöiden liikkuvuudesta syntyneitä tuottavuuden heijastusvaikutuksia (spillover effects) hyödyntäen suomalaisia yhdistettyjä työntekijä-työnantaja-aineistoja. Tulokset osoittavat, että tuottavammista toimipaikoista työntekijöiden palkkaamista seuraa tuottavuuden kasvua palkkaamista seuraavana vuonna. Varovaisimpana arviona tuottavuuslisäyksen suuruus on 0,45 prosenttia keskimääräiselle toimipaikalle. Havaittu yhteys tuottavuuden ja tuottavammista toimipaikoista palkkaamisen välillä säilyy useilla estimointispesifikaatioilla, eikä sitä voida selittää muutoksilla vastaanottavien toimipaikkojen inhimillisen pääoman määrissä.This dissertation includes three articles concerning the field of economics of management practices and productivity. The first article analyses the variation in the management practices across countries and across regions within a country. The quantitative establishment-level management scores show that Finnish management practices are only slightly behind the US and on par with those in Germany. With the Finnish data, we then perform an Olley-Pakes decomposition of the management score using a moment-based estimation procedure. The decomposition shows no statistically significant differences in the unweighted average scores between Finnish regions, but reveal some significant differences in the employment weighted averages (i.e. aggregate scores) that can be attributed to the differences in the allocation of the labour force between establishments within regions. The second article details how managerial human capital affects the relationship between productivity and quantitative management practices. The results imply that the productivity improvements associated with adopting more structured management practices vary with the levels of managerial human capital. Accounting for the interaction, a 10 percent increase in the management score is associated with an average of 7.1 percent higher labour productivity. Furthermore, management practices can account for more than 24 percent of the observed productivity dispersion. This is almost as much as information and communication technologies and more than both research and development and human capital. The third article uses linked employer-employee data from Finland to examine the mobility of workers between establishments as a source of productivity-affecting knowledge spillovers. I find evidence that hiring workers from more productive establishments leads to higher productivity in the following year. For an average establishment, this productivity increase amounts to 0.45 percent in the most conservative estimate. The observed productivity gains hold for a variety of specifications, and changes in the receiving establishments’ human capital stock are ruled out as an explanation

Management practices in Finnish manufacturing establishments : evidence from FMOP

Edistysaskeleet aineiston keräämisessä ovat nostaneet johtamiskäytännöt esiin osana vastausta kysymykseen tuottavuuseroista. Kvantitatiiviseen kyselytyökaluun perustuvat tutkimukset ovat löytäneet kumulatiivista näyttöä johtamiskäytäntöjen kyvystä selittää tuottavuuseroja. Kyseisen työkalun nimi on Management and Organizational Practices Survey. Tässä tutkielmassa tarkastellaan Suomen johtamis- ja organisaatiokäytäntöjen kyselyllä eli FMOP-kyselyllä kerätyn aineiston avulla Suomen tehdasteollisuuden toimipaikkojen johtamiskäytäntöjä. Tarkoituksena on selvittää, onko Suomessa tilastollisesti merkitseviä alueellisia eroja johtamiskäytäntöjen laadussa. Helsinki-Uusimaata verrataan muihin Suomen suuralueisiin. Työvoimapainotettu keskiarvo eli kokonaisjohtamispistemäärä jaetaan osate-kijöihin käyttäen Olleyn ja Pakesin (1996) staattista hajotelmaa. Nämä osatekijät ovat painottamaton johtamispistemäärän keskiarvo sekä niin kutsuttu allokaatiovaikutus. Hajotelma tehdään hyödyntäen momentteihin perustuvaa estimointimenetelmää, joka mahdollistaa tarkan tilastollisen päättelyn koskien hajotelman osia. Suomen tehdasteollisuuden toimipaikka-aineistosta ei löydetä tilastollisesti merkitseviä alueellisia eroja johtamiskäytäntöjen laadussa.Due to advances in data gathering, management practices have started to emerge as another piece in the empirical productivity puzzle. After the development of a quantitative survey tool named the Management and Organizational Practices Survey (MOPS), studies have found cumulating evidence for the significance of management practices in explaining productivity dispersion. Data collected with the recently conducted Finnish Management and Organizational Practices Survey (FMOP) is used to examine management practices in Finnish manufacturing establishments. Helsinki-Uusimaa is compared to the other large areas of Finland to determine whether there are significant cross-regional differences in the quality of management practices. An Olley-Pakes decomposition is used for a cross-regional comparison of the components of the aggregate (employment weighted) management score. Furthermore, a moment-based estimation procedure is utilized to allow for statistical inference about the components of the decomposition. No statistically significant cross-regional differences in the quality of man-agement practices are found in Finnish manufacturing establishments